Is RPS2 p.Ser77Phe (c.230C>T) pathogenic?

RPS2 p.Ser77Phe (c.230C>T) is classified Uncertain significance in RPS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-14). AlphaMissense: likely pathogenic (0.952); Very rare (popmax 0.00988%, sas).

How common is RPS2 p.Ser77Phe (c.230C>T) in the general population?

RPS2 p.Ser77Phe (c.230C>T) is very rare (popmax 0.00988%, sas) (gnomAD).

What do computational predictors say about RPS2 p.Ser77Phe (c.230C>T)?

AlphaMissense predicts likely pathogenic (score 0.952) — an in-silico prediction, not a clinical call.

RPS2 p.Ser77Phe

c.230C>T · rs761069719 · VCV2267076

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.952 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00988%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.952	likely pathogenic
REVEL	0.4	indeterminate
SaProt	LLR -13.29	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 9.9	GERP 0.81, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 1,352 bp · p 7.1e-06 · regional, not allelic
Overall
CADD	25.9	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 0.00988% South Asian · 9/91,080 alleles

Filtering AF 0.00514% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00375%

Overall 0.00211% 34/1,613,388 alleles · very rare exomes 31/1,461,160 · genomes 3/152,228 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00988%	10,120
Remaining individualsnot grpmax-eligible	0.0048%	20,825
African / African-American	0.00267%	37,465
European (non-Finnish)	0.0017%	58,992

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: RPS2
Protein: p.Ser77Phe
Coding: c.230C>T
MANE Select: NM_002952
dbSNP: rs761069719
Type: single nucleotide variant
Location: chr16:1964313 (GRCh38)
Gene constraint: LOEUF 0.493 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 82.10 · 204 PDB

Full RPS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RPS2 p.Arg46= Benign ★★ same type
RPS2 p.Ser85= Benign ★★ same type
RPS2 p.Ala198Ser Uncertain significance ★ ⚠ same type
RPS2 p.Ala291Thr Uncertain significance ★ ⚠ same type
RPS2 p.Ala5Gly Uncertain significance ★ ⚠ same type
RPS2 p.Ala8Pro Uncertain significance ★ ⚠ same type
RPS2 p.Ala8Val Uncertain significance ★ ⚠ same type
RPS2 p.Arg167Gly 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/rps2-p-ser77phe (accessed [today's date]).

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