Is ITGAM p.Arg413Gln (c.1238G>A) pathogenic?

ITGAM p.Arg413Gln (c.1238G>A) is classified Uncertain significance in ITGAM (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-03). AlphaMissense: likely benign (0.0816); Very rare (popmax 0.00536%, afr).

How common is ITGAM p.Arg413Gln (c.1238G>A) in the general population?

ITGAM p.Arg413Gln (c.1238G>A) is very rare (popmax 0.00536%, afr) (gnomAD).

What do computational predictors say about ITGAM p.Arg413Gln (c.1238G>A)?

AlphaMissense predicts likely benign (score 0.0816) — an in-silico prediction, not a clinical call.

ITGAM p.Arg413Gln

c.1238G>A · rs755777607 · VCV1415530

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0816 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00536%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0816	likely benign
REVEL	0.083	moderately benign-leaning
SaProt	LLR -5.07	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.89	acceptor gain · deltas
Pangolin	Δ0.50	gain · loss 0.23 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 0.62	GERP -0.29, phastCons 0.015
Regional constraint	o/e 0.91	unconstrained · MANE · 72 kb · p 0.00026 · regional, not allelic
Overall
CADD	23.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00536% African / African-American · 4/74,652 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000937% 15/1,601,462 alleles · very rare exomes 11/1,449,408 · genomes 4/152,054 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00536%	18,663
South Asian	0.00225%	44,350
Admixed American	0.00172%	58,128
Remaining individualsnot grpmax-eligible	0.00161%	62,068
European (non-Finnish)	0.000596%	167,739

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.Arg413Gln
Coding: c.1238G>A
MANE Select: NM_000632
dbSNP: rs755777607
Type: single nucleotide variant
Location: chr16:31277991 (GRCh38)
Gene constraint: LOEUF 0.678 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.30 · 31 PDB
Residue 413: a β-strand

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

Similar variants

ITGAM p.Arg413Trp 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-arg413gln (accessed [today's date]).

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