Is SRM p.Ala9Pro (c.25G>C) pathogenic?

SRM p.Ala9Pro (c.25G>C) is classified Uncertain significance in SRM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-04). AlphaMissense: likely benign (0.0908); No allele count reported in gnomAD v4.1 (AN 1,260,480).

How common is SRM p.Ala9Pro (c.25G>C) in the general population?

SRM p.Ala9Pro (c.25G>C) is no allele count reported in gnomAD v4.1 (AN 1,260,480) (gnomAD).

What do computational predictors say about SRM p.Ala9Pro (c.25G>C)?

AlphaMissense predicts likely benign (score 0.0908) — an in-silico prediction, not a clinical call.

SRM p.Ala9Pro

c.25G>C · VCV4589545

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0908 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,260,480)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0908	likely benign
REVEL	0.166	moderately benign-leaning
SaProt	LLR -6.39	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.14	GERP 0.29, phastCons 0.001
Regional constraint	o/e 0.60	unconstrained · MANE · 5,075 bp · p 3.2e-16 · regional, not allelic
Overall
CADD	18.02	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

No allele count reported in gnomAD v4.1 (AN 1,260,480). 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: SRM
Protein: p.Ala9Pro
Coding: c.25G>C
MANE Select: NM_003132
Type: single nucleotide variant
Location: chr1:11059919 (GRCh38)
Gene constraint: LOEUF 0.593 · pLI 0.64 (gnomAD)
Structure: AlphaFold pLDDT 94.64 · 6 PDB
Residue 9: an α-helix

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

Similar variants

SRM p.Ala15Val Uncertain significance ★ ⚠ same type
SRM p.Ala272Thr Uncertain significance ★ ⚠ same type
SRM p.Ala287Thr Uncertain significance ★ same type
SRM p.Ala84Ser Uncertain significance ★ ⚠ same type
SRM p.Arg17Cys Uncertain significance ★ ⚠ same type
SRM p.Arg285Cys Uncertain significance ★ ⚠ same type
SRM p.Arg285His Uncertain significance ★ ⚠ same type
SRM p.Arg295His 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/srm-p-ala9pro (accessed [today's date]).

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