Is RPL17 p.Trp76Cys (c.228G>T) pathogenic?

RPL17 p.Trp76Cys (c.228G>T) is classified Uncertain significance in RPL17 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-18). AlphaMissense: likely pathogenic (0.9213); Very rare (popmax 6.2e-05%).

How common is RPL17 p.Trp76Cys (c.228G>T) in the general population?

RPL17 p.Trp76Cys (c.228G>T) is very rare (popmax 6.2e-05%) (gnomAD).

What do computational predictors say about RPL17 p.Trp76Cys (c.228G>T)?

AlphaMissense predicts likely pathogenic (score 0.9213) — an in-silico prediction, not a clinical call.

RPL17 p.Trp76Cys

c.228G>T · VCV3947455

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9213 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9213	likely pathogenic
REVEL	0.542	indeterminate
SaProt	LLR -14.99	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.9, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 2,057 bp · p 0.00044 · regional, not allelic
Overall
CADD	27.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.2e-05%

Overall 6.2e-05% 1/1,613,972 alleles · very rare exomes 1/1,461,712 · genomes 0/152,260 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: RPL17
Protein: p.Trp76Cys
Coding: c.228G>T
MANE Select: NM_001035006
Type: single nucleotide variant
Location: chr18:49490541 (GRCh38)
Gene constraint: LOEUF 0.184 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 91.85 · 184 PDB
Residue 76: an α-helix

Full RPL17 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RPL23 p.Arg89Gly Uncertain significance ★★ ⚠ same type
RPL23 p.Arg89His Uncertain significance ★★ ⚠ same type
RPL23 p.Ile132Val Uncertain significance ★★ ⚠ same type
RPL17 p.Arg30His Uncertain significance ★ ⚠ same type
RPL17 p.Arg42Gln Uncertain significance ★ ⚠ same type
RPL17 p.Arg62Gly Uncertain significance ★ ⚠ same type
RPL17 p.Asn64Ser Uncertain significance ★ ⚠ same type
RPL17 p.Gln56Leu Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/rpl17-p-trp76cys (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown