Is ITGAM p.Cys1027Phe (c.3080G>T) pathogenic?

ITGAM p.Cys1027Phe (c.3080G>T) is classified Uncertain significance in ITGAM (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-22). AlphaMissense: likely pathogenic (0.7507); Absent from gnomAD v4.1.

How common is ITGAM p.Cys1027Phe (c.3080G>T) in the general population?

ITGAM p.Cys1027Phe (c.3080G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ITGAM p.Cys1027Phe (c.3080G>T)?

AlphaMissense predicts likely pathogenic (score 0.7507) — an in-silico prediction, not a clinical call.

ITGAM p.Cys1027Phe

c.3080G>T · rs2080563673 · VCV2011149

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7507 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7507	likely pathogenic
REVEL	0.615	indeterminate
SaProt	LLR -14.60	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	Δ0.60	acceptor gain · deltas
Pangolin	Δ0.30	gain · loss 0.04 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 9.8	GERP 2.2, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 72 kb · p 0.00026 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ITGAM
Protein: p.Cys1027Phe
Coding: c.3080G>T
MANE Select: NM_000632
dbSNP: rs2080563673
Type: single nucleotide variant
Location: chr16:31330327 (GRCh38)
Gene constraint: LOEUF 0.678 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.30 · 31 PDB
Residue 1027: a β-strand; a disulfide bond

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-cys1027phe (accessed [today's date]).

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