Is MYSM1 p.Ile331Val (c.991A>G) pathogenic?

MYSM1 p.Ile331Val (c.991A>G) is classified Uncertain significance in MYSM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-07). AlphaMissense: likely benign (0.0658); Absent from gnomAD v4.1.

How common is MYSM1 p.Ile331Val (c.991A>G) in the general population?

MYSM1 p.Ile331Val (c.991A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MYSM1 p.Ile331Val (c.991A>G)?

AlphaMissense predicts likely benign (score 0.0658) — an in-silico prediction, not a clinical call.

MYSM1 p.Ile331Val

c.991A>G · rs2100649374 · VCV1517956

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0658 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0658	likely benign
REVEL	0.013	strongly benign-leaning
SaProt	LLR -6.18	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 -3.3	GERP -4.3
Regional constraint	o/e 1.00	unconstrained · MANE · 28 kb · p 0.95 · regional, not allelic
Overall
CADD	0.004	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

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: MYSM1
Protein: p.Ile331Val
Coding: c.991A>G
MANE Select: NM_001085487
dbSNP: rs2100649374
Type: single nucleotide variant
Location: chr1:58682053 (GRCh38)
Gene constraint: LOEUF 0.578 · pLI 0.09 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 64.69 · 2 PDB

Full MYSM1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MYSM1 p.Arg506Ter Pathogenic ★★ same type
MYSM1 p.Gln629Ter Pathogenic ★★ same type
MYSM1 p.Arg138Gln Uncertain significance ★★ ⚠ same type
MYSM1 p.Arg150Cys Uncertain significance ★★ ⚠ same type
MYSM1 p.Arg204Cys Uncertain significance ★★ ⚠ same type
MYSM1 p.Arg478Gln Uncertain significance ★★ ⚠ same type
MYSM1 p.Arg494His Uncertain significance ★★ ⚠ same type
MYSM1 p.Arg499His 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/mysm1-p-ile331val (accessed [today's date]).

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