Is ITGAM p.Arg844Cys (c.2530C>T) pathogenic?

ITGAM p.Arg844Cys (c.2530C>T) is classified Likely benign in ITGAM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-08). AlphaMissense: likely benign (0.2647); Rare (popmax 0.178%, amr).

How common is ITGAM p.Arg844Cys (c.2530C>T) in the general population?

ITGAM p.Arg844Cys (c.2530C>T) is rare (popmax 0.178%, amr) (gnomAD).

What do computational predictors say about ITGAM p.Arg844Cys (c.2530C>T)?

AlphaMissense predicts likely benign (score 0.2647) — an in-silico prediction, not a clinical call.

ITGAM p.Arg844Cys

c.2530C>T · rs199694320 · VCV1149124

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2647 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.178%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2647	likely benign
REVEL	0.101	moderately benign-leaning
SaProt	LLR -11.27	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.4	GERP -3.5
Regional constraint	o/e 0.91	unconstrained · MANE · 72 kb · p 0.00026 · regional, not allelic
Overall
CADD	18.36	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.178% Admixed American · 107/60,014 alleles

Filtering AF 0.151% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.141%

Overall 0.00836% 135/1,613,972 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.178%	561
Remaining individualsnot grpmax-eligible	0.008%	12,497
East Asian	0.00223%	44,880
European (non-Finnish)	0.00186%	53,631

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.Arg844Cys
Coding: c.2530C>T
MANE Select: NM_000632
dbSNP: rs199694320
Type: single nucleotide variant
Location: chr16:31325524 (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 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-arg844cys (accessed [today's date]).

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