Is RPSA p.Pro236Ser (c.706C>T) pathogenic?

RPSA p.Pro236Ser (c.706C>T) is classified Uncertain significance in RPSA (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-28). AlphaMissense: likely benign (0.1255); Very rare (popmax 0.004%, afr).

How common is RPSA p.Pro236Ser (c.706C>T) in the general population?

RPSA p.Pro236Ser (c.706C>T) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about RPSA p.Pro236Ser (c.706C>T)?

AlphaMissense predicts likely benign (score 0.1255) — an in-silico prediction, not a clinical call.

RPSA p.Pro236Ser

c.706C>T · rs780597250 · VCV1349805

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1255 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1255	likely benign
REVEL	0.058	moderately benign-leaning
SaProt	LLR -12.29	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.4, phastCons 1
Regional constraint	o/e 0.39	unconstrained · MANE · 1,432 bp · p 9.8e-18 · regional, not allelic
Overall
CADD	25.6	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,920 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000312% 5/1,601,974 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,973
Remaining individualsnot grpmax-eligible	0.0016%	62,404
European (non-Finnish)	8.47e-05%	1,179,942

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: RPSA
Protein: p.Pro236Ser
Coding: c.706C>T
MANE Select: NM_002295
dbSNP: rs780597250
Type: single nucleotide variant
Location: chr3:39411974 (GRCh38)
Gene constraint: LOEUF 0.144 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.45 · 204 PDB

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

Similar variants

RPSA p.Arg191Cys Uncertain significance ★★ ⚠ same type
RPSA p.Ile145Val Uncertain significance ★★ ⚠ same type
RPSA c.134-14C>T Likely benign ★★ same type
RPSA c.134-32C>T Benign ★★ same type
RPSA c.252+17T>C Benign/Likely benign ★★ same type
RPSA c.627+10T>C Likely benign ★★ same type
RPSA c.628-17T>C Likely benign ★★ same type
RPSA c.-8T>C Benign/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/rpsa-p-pro236ser (accessed [today's date]).

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