Is ITGAM p.Leu601= (c.1801C>T) pathogenic?

ITGAM p.Leu601= (c.1801C>T) is classified Benign in ITGAM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-01). Common (popmax 19.8%, afr) — too common for a highly-penetrant pathogenic allele.

ITGAM p.Leu601=

Q: How common is ITGAM p.Leu601= (c.1801C>T) in the general population?

ITGAM p.Leu601= (c.1801C>T) is common (popmax 19.8%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1801C>T · rs8056264 · VCV1170587

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 19.8%, afr) — too common for a highly-penetrant pathogenic allele

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 0.41	GERP -4.6, phastCons 0.86
Overall
CADD	3.203	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 19.8% African / African-American · 14,844/74,972 alleles

Filtering AF 19.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 19.4%

Overall 1.06% 17,080/1,613,940 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	19.8%	5
Admixed American	1.39%	72
Remaining individualsnot grpmax-eligible	1.35%	74
Middle Eastern	0.429%	233
South Asian	0.0494%	2,024
European (non-Finnish)	0.041%	2,438
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,803

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.Leu601=
Coding: c.1801C>T
MANE Select: NM_000632
dbSNP: rs8056264
Type: single nucleotide variant
Location: chr16:31321334 (GRCh38)
Gene constraint: LOEUF 0.678 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.30 · 31 PDB
Residue 601: 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-leu601 (accessed [today's date]).

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