Is SRM p.Pro115Ala (c.343C>G) pathogenic?

SRM p.Pro115Ala (c.343C>G) is classified Uncertain significance in SRM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-25). AlphaMissense: likely benign (0.0831); Absent from gnomAD v4.1.

How common is SRM p.Pro115Ala (c.343C>G) in the general population?

SRM p.Pro115Ala (c.343C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SRM p.Pro115Ala (c.343C>G)?

AlphaMissense predicts likely benign (score 0.0831) — an in-silico prediction, not a clinical call.

SRM p.Pro115Ala

c.343C>G · VCV4174852

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0831 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0831	likely benign
REVEL	0.286	benign-leaning
SaProt	LLR -10.23	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3	GERP 0.22, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 5,075 bp · p 3.2e-16 · regional, not allelic
Overall
CADD	19.11	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SRM
Protein: p.Pro115Ala
Coding: c.343C>G
MANE Select: NM_003132
Type: single nucleotide variant
Location: chr1:11058838 (GRCh38)
Gene constraint: LOEUF 0.593 · pLI 0.64 (gnomAD)
Structure: AlphaFold pLDDT 94.64 · 6 PDB
Residue 115: the pabs domain

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.Ala9Pro 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

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-pro115ala (accessed [today's date]).

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