Is ITGAM p.Val85Met (c.253G>A) pathogenic?

ITGAM p.Val85Met (c.253G>A) is classified Uncertain significance in ITGAM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-11-01). AlphaMissense: likely benign (0.1267); Very rare (popmax 0.00667%, amr).

How common is ITGAM p.Val85Met (c.253G>A) in the general population?

ITGAM p.Val85Met (c.253G>A) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about ITGAM p.Val85Met (c.253G>A)?

AlphaMissense predicts likely benign (score 0.1267) — an in-silico prediction, not a clinical call.

ITGAM p.Val85Met

c.253G>A · rs1478334387 · VCV1355903

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1267 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1267	likely benign
REVEL	0.425	indeterminate
SaProt	LLR -7.14	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.3	GERP 2.1, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 72 kb · p 0.00026 · regional, not allelic
Overall
CADD	20.4	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 0.00667% Admixed American · 4/59,984 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.00112% 18/1,613,776 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	14,996
South Asian	0.00329%	30,356
East Asian	0.00223%	44,868
European (non-Finnish)	0.000847%	117,996

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: ITGAM
Protein: p.Val85Met
Coding: c.253G>A
MANE Select: NM_000632
dbSNP: rs1478334387
Type: single nucleotide variant
Location: chr16:31265825 (GRCh38)
Gene constraint: LOEUF 0.678 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.30 · 31 PDB

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

Similar variants

ITGAM p.Val85Leu Uncertain significance ★ ⚠ same residue
ITGAM c.704+5G>A Uncertain significance ★★ same type
ITGAM p.Ala31Thr Uncertain significance ★★ ⚠ same type
ITGAM p.Ala433Val Uncertain significance ★★ ⚠ same type
ITGAM p.Ala753Val Uncertain significance ★★ ⚠ same type
ITGAM p.Ala943Val Uncertain significance ★★ ⚠ same type
ITGAM p.Arg1003His Uncertain significance ★★ ⚠ same type
ITGAM p.Arg131Trp 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/itgam-p-val85met (accessed [today's date]).

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