Is RPL3 p.Pro33Arg (c.98C>G) pathogenic?

RPL3 p.Pro33Arg (c.98C>G) is classified Uncertain significance in RPL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-07). AlphaMissense: likely pathogenic (0.9942); Very rare (popmax 0.00333%, amr).

How common is RPL3 p.Pro33Arg (c.98C>G) in the general population?

RPL3 p.Pro33Arg (c.98C>G) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about RPL3 p.Pro33Arg (c.98C>G)?

AlphaMissense predicts likely pathogenic (score 0.9942) — an in-silico prediction, not a clinical call.

RPL3 p.Pro33Arg

c.98C>G · VCV3947486

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9942 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9942	likely pathogenic
REVEL	0.614	indeterminate
SaProt	LLR -12.99	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.7	GERP 2, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 3,033 bp · p 0.15 · regional, not allelic
Overall
CADD	29.7	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 0.00333% Admixed American · 2/60,000 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000496% 8/1,613,986 alleles · very rare exomes 8/1,461,714 · genomes 0/152,272 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,000
African / African-American	0.00133%	75,028
European (non-Finnish)	0.000424%	235,988

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: RPL3
Protein: p.Pro33Arg
Coding: c.98C>G
MANE Select: NM_000967
Type: single nucleotide variant
Location: chr22:39318498 (GRCh38)
Gene constraint: LOEUF 0.165 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 96.38 · 182 PDB
Residue 33: the 'disordered' region; an α-helix

Full RPL3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RPL3 p.Pro37= Benign ★★ same type
RPL3 p.Ala197Thr Uncertain significance ★ ⚠ same type
RPL3 p.Ala398Gly Uncertain significance ★ ⚠ same type
RPL3 p.Arg161His Uncertain significance ★ ⚠ same type
RPL3 p.Arg169Cys Uncertain significance ★ same type
RPL3 p.Arg174His Uncertain significance ★ ⚠ same type
RPL3 p.Arg242His Uncertain significance ★ ⚠ same type
RPL3 p.Arg277Cys 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/rpl3-p-pro33arg (accessed [today's date]).

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