Is ITGAM p.Val82Met (c.244G>A) pathogenic?

ITGAM p.Val82Met (c.244G>A) is classified Conflicting classifications of pathogenicity in ITGAM (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-04-21). AlphaMissense: likely benign (0.0817); Ultra-rare (popmax 0.0534%, afr).

How common is ITGAM p.Val82Met (c.244G>A) in the general population?

ITGAM p.Val82Met (c.244G>A) is ultra-rare (popmax 0.0534%, afr) (gnomAD).

What do computational predictors say about ITGAM p.Val82Met (c.244G>A)?

AlphaMissense predicts likely benign (score 0.0817) — an in-silico prediction, not a clinical call.

ITGAM p.Val82Met

c.244G>A · rs373322978 · VCV1419004

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0817 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0534%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0817	likely benign
REVEL	0.104	moderately benign-leaning
SaProt	LLR -7.63	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.3	GERP -2.5
Regional constraint	o/e 0.91	unconstrained · MANE · 72 kb · p 0.00026 · regional, not allelic
Overall
CADD	11.97	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

Grpmax group 0.0534% African / African-American · 40/74,868 alleles

Filtering AF 0.0402% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0357%

Overall 0.00328% 53/1,613,702 alleles · ultra-rare exomes 30/1,461,678 · genomes 23/152,024 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0534%	1,872
South Asian	0.00549%	18,214
Admixed American	0.005%	19,992
Remaining individualsnot grpmax-eligible	0.0016%	62,462
Finnishnot grpmax-eligible	0.00156%	63,972
European (non-Finnish)	0.000254%	393,317

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.Val82Met
Coding: c.244G>A
MANE Select: NM_000632
dbSNP: rs373322978
Type: single nucleotide variant
Location: chr16:31265816 (GRCh38)

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

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-val82met (accessed [today's date]).

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