Is STOM p.Ile44Arg (c.131T>G) pathogenic?

STOM p.Ile44Arg (c.131T>G) is classified Uncertain significance in STOM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-13). AlphaMissense: likely pathogenic (0.9354); Absent from gnomAD v4.1.

How common is STOM p.Ile44Arg (c.131T>G) in the general population?

STOM p.Ile44Arg (c.131T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about STOM p.Ile44Arg (c.131T>G)?

AlphaMissense predicts likely pathogenic (score 0.9354) — an in-silico prediction, not a clinical call.

STOM p.Ile44Arg

c.131T>G · VCV3963472

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9354 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9354	likely pathogenic
REVEL	0.739	pathogenic-leaning
SaProt	LLR -16.41	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 1.9, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 29 kb · p 0.00013 · regional, not allelic
Overall
CADD	21.9	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

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: STOM
Protein: p.Ile44Arg
Coding: c.131T>G
MANE Select: NM_004099
Type: single nucleotide variant
Location: chr9:121356087 (GRCh38)
Gene constraint: LOEUF 1.126 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.37 · 8 PDB
Residue 44: an α-helix

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

Similar variants

STOM p.Gly278Glu Uncertain significance ★★ ⚠ same type
STOM p.Thr266Ala Uncertain significance ★★ ⚠ same type
STOM p.Val126Ile Uncertain significance ★★ ⚠ same type
STOM p.Ala139Thr Uncertain significance ★ ⚠ same type
STOM p.Ala213Val Uncertain significance ★ ⚠ same type
STOM p.Ala36Val Uncertain significance ★ ⚠ same type
STOM p.Ala63Gly Uncertain significance ★ ⚠ same type
STOM p.Ala63Thr 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/stom-p-ile44arg (accessed [today's date]).

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