RPL3L Variant Explorer
Pathogenicity predictions from AlphaMissense (Cheng et al., Science 2023)
for all 2,400 possible missense amino-acid substitutions in RPL3L (canonical transcript
ENST00000268661.8 / NM_005061, 407 aa), cross-referenced with gnomAD v4 population frequencies
and variants observed in CMD2D. Search by position (e.g., 27) or variant (e.g., G27D);
click the Position or AM score headers to sort.
How to read this table — and how not to
AlphaMissense predicts general missense deleteriousness, not CMD2D. The disease mechanism is specific: recurrent hotspot variants are toxic because they combine loss of function with preservation of RPL3L's repression of RPL3 — a property no sequence-based predictor captures. Note that several confirmed CMD2D alleles (e.g., p.Thr189Met, p.Arg58Gln, p.Glu202Gly) are predicted benign — exactly as the dual loss-/gain-of-function model predicts for non-hotspot alleles, which lose RPL3L function without blocking RPL3 compensation. A "likely pathogenic" prediction also does not mean a variant causes CMD2D: biallelic inheritance and rarity are required too. The most useful shortlist is high AM score + absent from gnomAD (use the frequency filter below). Predictions are a research aid, not clinical evidence — see the curated allele table for experimentally characterized variants.
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AM pathogenicity score 0 (benign) → 1 (pathogenic)
| Position | Variant | AM score | Class | gnomAD | Observed in |
|---|
Data: AlphaMissense predictions (DeepMind Technologies Limited; CC BY 4.0), canonical transcript ENST00000268661.8, GRCh38. Classification thresholds: likely_benign < 0.34 < ambiguous < 0.564 < likely_pathogenic. Frequencies: gnomAD v4 (exome + genome allele counts combined; "absent" = variant not found in gnomAD v4). AlphaMissense has not been validated for, and is not approved for, any clinical use. Observed-variant annotations are summarized from the primary literature (see For Researchers).