Is ITGAM p.Val975Asp (c.2924T>A) pathogenic?

ITGAM p.Val975Asp (c.2924T>A) is classified Uncertain significance in ITGAM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-08). AlphaMissense: ambiguous (0.3619); Very rare (popmax 0.00383%, amr).

How common is ITGAM p.Val975Asp (c.2924T>A) in the general population?

ITGAM p.Val975Asp (c.2924T>A) is very rare (popmax 0.00383%, amr) (gnomAD).

What do computational predictors say about ITGAM p.Val975Asp (c.2924T>A)?

AlphaMissense predicts ambiguous (score 0.3619) — an in-silico prediction, not a clinical call.

ITGAM p.Val975Asp

c.2924T>A · VCV3861634

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3619 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00383%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3619	ambiguous
REVEL	0.253	benign-leaning
SaProt	LLR -7.68	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP 2.1, phastCons 0.006
Regional constraint	o/e 0.91	unconstrained · MANE · 72 kb · p 0.00026 · regional, not allelic
Overall
CADD	18.69	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 0.00383% Admixed American · 2/52,160 alleles

Filtering AF 0.000636% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000238%

Overall 0.000192% 3/1,564,812 alleles · very rare exomes 3/1,412,604 · genomes 0/152,208 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00383%	26,080
European (non-Finnish)	8.66e-05%	1,154,684

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.Val975Asp
Coding: c.2924T>A
MANE Select: NM_000632
Type: single nucleotide variant
Location: chr16:31329853 (GRCh38)
Gene constraint: LOEUF 0.678 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.30 · 31 PDB
Residue 975: a β-strand

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

Similar variants

ITGAM p.Val975Ile Conflicting classifications of pathogenicity ★ ⚠ 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-val975asp (accessed [today's date]).

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