Is RPS3 p.Pro237Ser (c.709C>T) pathogenic?

RPS3 p.Pro237Ser (c.709C>T) is classified Uncertain significance in RPS3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-07). AlphaMissense: likely benign (0.0989); Ultra-rare (popmax 0.0165%, mid).

How common is RPS3 p.Pro237Ser (c.709C>T) in the general population?

RPS3 p.Pro237Ser (c.709C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about RPS3 p.Pro237Ser (c.709C>T)?

AlphaMissense predicts likely benign (score 0.0989) — an in-silico prediction, not a clinical call.

RPS3 p.Pro237Ser

c.709C>T · VCV4579513

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0989 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.0989	likely benign
REVEL	0.303	indeterminate
SaProt	LLR -7.98	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.28	constrained · MANE · 4,145 bp · p 5.7e-34 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0165% Middle Eastern · 1/6,074 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.000434% 7/1,612,708 alleles · ultra-rare exomes 4/1,460,508 · genomes 3/152,200 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,074
African / African-American	0.00667%	14,984
Admixed American	0.00167%	59,900

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: RPS3
Protein: p.Pro237Ser
Coding: c.709C>T
MANE Select: NM_001005
Type: single nucleotide variant
Location: chr11:75404842 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 91.39 · 197 PDB
Residue 237: the 'disordered' region

Full RPS3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RPS3 c.162-3C>T Benign ★★ same type
RPS3 p.Met189Val Uncertain significance ★ ⚠ same type
RPS3 p.Phe77Cys Uncertain significance ★ ⚠ same type
RPS3 p.Pro233Leu Uncertain significance ★ ⚠ same type
RPS3 p.Tyr34Cys Uncertain significance ★ ⚠ same type
RPS3 p.Arg54= Likely benign ★ 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/rps3-p-pro237ser (accessed [today's date]).

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