Is ITGAM p.Thr761= (c.2283A>G) pathogenic?

ITGAM p.Thr761= (c.2283A>G) is classified Likely benign in ITGAM (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-20). Very rare (popmax 0.00137%, afr).

How common is ITGAM p.Thr761= (c.2283A>G) in the general population?

ITGAM p.Thr761= (c.2283A>G) is very rare (popmax 0.00137%, afr) (gnomAD).

ITGAM p.Thr761=

c.2283A>G · rs371569571 · VCV1381283

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00137%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.5	GERP -4.4
Overall
CADD	1.845	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00137% African / African-American · 1/72,772 alleles

Filtering AF 0.000512% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000374%

Overall 0.000772% 12/1,555,316 alleles · very rare exomes 10/1,403,184 · genomes 2/152,132 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00137%	72,772
European (non-Finnish)	0.000954%	104,868

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.Thr761=
Coding: c.2283A>G
MANE Select: NM_000632
dbSNP: rs371569571
Type: single nucleotide variant
Location: chr16:31324776 (GRCh38)
Gene constraint: LOEUF 0.678 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.30 · 31 PDB
Residue 761: a β-strand

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

Similar variants

ITGAM p.Thr761Ile Uncertain significance ★ ⚠ same residue
ITGAM p.Thr761Pro 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

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-thr761 (accessed [today's date]).

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