Is ITGAM p.Tyr64= (c.192C>T) pathogenic?

ITGAM p.Tyr64= (c.192C>T) is classified Likely benign in ITGAM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-24). Ultra-rare (popmax 0.0829%, afr).

How common is ITGAM p.Tyr64= (c.192C>T) in the general population?

ITGAM p.Tyr64= (c.192C>T) is ultra-rare (popmax 0.0829%, afr) (gnomAD).

ITGAM p.Tyr64=

c.192C>T · rs373413258 · VCV735533

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0829%, 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 0.11	GERP 0.21, phastCons 0.3
Overall
CADD	5.526	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0829% African / African-American · 62/74,784 alleles

Filtering AF 0.0663% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0604%

Overall 0.0051% 82/1,607,938 alleles · ultra-rare exomes 31/1,455,788 · genomes 51/152,150 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0829%	1,206
Admixed American	0.0118%	8,459
Remaining individualsnot grpmax-eligible	0.00322%	31,085
European (non-Finnish)	0.000934%	107,051

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.Tyr64=
Coding: c.192C>T
MANE Select: NM_000632
dbSNP: rs373413258
Type: single nucleotide variant
Location: chr16:31265452 (GRCh38)
Gene constraint: LOEUF 0.678 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.30 · 31 PDB
Residue 64: a β-strand

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

Similar variants

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
ITGAM p.Arg224Trp 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-tyr64 (accessed [today's date]).

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