Is OSM p.Val3Ile (c.7G>A) pathogenic?

OSM p.Val3Ile (c.7G>A) is classified Uncertain significance in OSM (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-26). AlphaMissense: likely benign (0.1153); Very rare (popmax 0.000254%, nfe).

How common is OSM p.Val3Ile (c.7G>A) in the general population?

OSM p.Val3Ile (c.7G>A) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about OSM p.Val3Ile (c.7G>A)?

AlphaMissense predicts likely benign (score 0.1153) — an in-silico prediction, not a clinical call.

OSM p.Val3Ile

c.7G>A · rs1929403181 · VCV2303172

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1153 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1153	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -6.76	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 -0.28	GERP 0.34, phastCons 0.18
Regional constraint	o/e 0.96	unconstrained · MANE · 2,913 bp · p 0.48 · regional, not allelic
Overall
CADD	5.744	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

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,340 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,612,924 alleles · very rare exomes 3/1,460,640 · genomes 0/152,284 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: OSM
Protein: p.Val3Ile
Coding: c.7G>A
MANE Select: NM_020530
dbSNP: rs1929403181
Type: single nucleotide variant
Location: chr22:30266793 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI 0.55 (gnomAD)
Structure: AlphaFold pLDDT 79.50 · 5 PDB

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

Similar variants

OSM p.Gln97Ter Likely pathogenic ★ same type
OSM p.Ala101Asp Uncertain significance ★ ⚠ same type
OSM p.Ala120Val Uncertain significance ★ ⚠ same type
OSM p.Ala23Val Uncertain significance ★ ⚠ same type
OSM p.Ala26Val Uncertain significance ★ ⚠ same type
OSM p.Arg116Cys Uncertain significance ★ ⚠ same type
OSM p.Arg170Gln Uncertain significance ★ ⚠ same type
OSM p.Arg187Cys 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/osm-p-val3ile (accessed [today's date]).

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