Is ITGAM p.Ile429= (c.1287C>T) pathogenic?

ITGAM p.Ile429= (c.1287C>T) is classified Likely benign in ITGAM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-02). Ultra-rare (popmax 0.0187%, afr).

How common is ITGAM p.Ile429= (c.1287C>T) in the general population?

ITGAM p.Ile429= (c.1287C>T) is ultra-rare (popmax 0.0187%, afr) (gnomAD).

ITGAM p.Ile429=

c.1287C>T · rs770023345 · VCV1554017

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, 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 -8.9	GERP -3.7
Overall
CADD	1.421	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0187% African / African-American · 14/74,774 alleles

Filtering AF 0.0112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00906%

Overall 0.00224% 36/1,607,412 alleles · ultra-rare exomes 22/1,455,286 · genomes 14/152,126 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0187%	5,341
East Asian	0.00672%	14,879
Finnishnot grpmax-eligible	0.00629%	15,904
Remaining individualsnot grpmax-eligible	0.00482%	20,763
European (non-Finnish)	0.00102%	98,092

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.Ile429=
Coding: c.1287C>T
MANE Select: NM_000632
dbSNP: rs770023345
Type: single nucleotide variant
Location: chr16:31278040 (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.Ile429Val 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-ile429 (accessed [today's date]).

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