Is ITGAM p.Arg415Trp (c.1243C>T) pathogenic?

ITGAM p.Arg415Trp (c.1243C>T) is classified Likely benign in ITGAM (ClinVar, Single submitter, 2 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.1445); Rare (popmax 0.139%, nfe).

How common is ITGAM p.Arg415Trp (c.1243C>T) in the general population?

ITGAM p.Arg415Trp (c.1243C>T) is rare (popmax 0.139%, nfe) (gnomAD).

What do computational predictors say about ITGAM p.Arg415Trp (c.1243C>T)?

AlphaMissense predicts likely benign (score 0.1445) — an in-silico prediction, not a clinical call.

ITGAM p.Arg415Trp

c.1243C>T · rs192388678 · VCV1158783

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1445 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.139%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1445	likely benign
REVEL	0.093	moderately benign-leaning
SaProt	LLR -11.52	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.41 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.99	GERP -0.28
Regional constraint	o/e 0.91	unconstrained · MANE · 72 kb · p 0.00026 · regional, not allelic
Overall
CADD	17.64	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 0.139% European (non-Finnish) · 1,638/1,174,612 alleles

Filtering AF 0.134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.132%

Overall 0.122% 1,954/1,602,556 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.251%	398
European (non-Finnish)grpmax	0.139%	717
Remaining individualsnot grpmax-eligible	0.124%	807
Admixed American	0.0909%	1,100
African / African-American	0.0254%	3,936
South Asian	0.00675%	14,810
Ashkenazi Jewishnot grpmax-eligible	0.00341%	29,286
East Asian	0.00225%	44,400

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg415Trp
Coding: c.1243C>T
MANE Select: NM_000632
dbSNP: rs192388678
Type: single nucleotide variant
Location: chr16:31277996 (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.Arg415Gln 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-arg415trp (accessed [today's date]).

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