Is ITGAM p.Asp592= (c.1776C>T) pathogenic?

ITGAM p.Asp592= (c.1776C>T) is classified Likely benign in ITGAM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-08). Ultra-rare (popmax 0.0703%, sas).

How common is ITGAM p.Asp592= (c.1776C>T) in the general population?

ITGAM p.Asp592= (c.1776C>T) is ultra-rare (popmax 0.0703%, sas) (gnomAD).

ITGAM p.Asp592=

c.1776C>T · rs779418225 · VCV1912161

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0703%, sas)

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 -1	GERP -3.1, phastCons 0.002
Overall
CADD	7.312	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0703% South Asian · 64/91,086 alleles

Filtering AF 0.0564% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0514%

Overall 0.00403% 65/1,614,040 alleles · ultra-rare exomes 61/1,461,712 · genomes 4/152,328 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0703%	1,423
Remaining individualsnot grpmax-eligible	0.0016%	62,486

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.Asp592=
Coding: c.1776C>T
MANE Select: NM_000632
dbSNP: rs779418225
Type: single nucleotide variant
Location: chr16:31321309 (GRCh38)
Gene constraint: LOEUF 0.678 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.30 · 31 PDB
Residue 592: a binding site

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

Similar variants

ITGAM p.Asp592Glu 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-asp592 (accessed [today's date]).

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