Is RPSA p.Pro258Ser (c.772C>T) pathogenic?

RPSA p.Pro258Ser (c.772C>T) is classified Uncertain significance in RPSA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-14). AlphaMissense: ambiguous (0.3507); No allele count reported in gnomAD v4.1 (AN 1,610,680).

How common is RPSA p.Pro258Ser (c.772C>T) in the general population?

RPSA p.Pro258Ser (c.772C>T) is no allele count reported in gnomAD v4.1 (AN 1,610,680) (gnomAD).

What do computational predictors say about RPSA p.Pro258Ser (c.772C>T)?

AlphaMissense predicts ambiguous (score 0.3507) — an in-silico prediction, not a clinical call.

RPSA p.Pro258Ser

c.772C>T · rs2470587488 · VCV3000971

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3507 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,610,680)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3507	ambiguous
REVEL	0.166	moderately benign-leaning
SaProt	LLR -12.75	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.8	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	25.8	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

No allele count reported in gnomAD v4.1 (AN 1,610,680). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: RPSA
Protein: p.Pro258Ser
Coding: c.772C>T
MANE Select: NM_002295
dbSNP: rs2470587488
Type: single nucleotide variant
Location: chr3:39412040 (GRCh38)
Gene constraint: LOEUF 0.144 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.45 · 204 PDB
Residue 258: the 'laminin-binding' region

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

Similar variants

RPSA p.Pro258= Likely benign ★ same residue
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

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-pro258ser (accessed [today's date]).

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