Is ITGAM p.Ala423fs (c.1267dup) pathogenic?

ITGAM p.Ala423fs (c.1267dup) is classified Uncertain significance in ITGAM (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-20). No gnomAD frequency available for this variant.

How common is ITGAM p.Ala423fs (c.1267dup) in the general population?

ITGAM p.Ala423fs (c.1267dup) is no gnomAD frequency available for this variant (gnomAD).

ITGAM p.Ala423fs

c.1267dup · rs2144314694 · VCV1393641

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 12 of 30
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.1	GERP 1.9, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ITGAM
Protein: p.Ala423fs
Coding: c.1267dup
MANE Select: NM_000632
dbSNP: rs2144314694
Type: Duplication
Location: chr16:31278015 (GRCh38)
Gene constraint: LOEUF 0.678 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.30 · 31 PDB
Residue 423: a β-strand

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

Similar variants

ITGAM p.Ala423Thr Uncertain significance ★ ⚠ same residue
ITGAM c.238_238+3dup Uncertain significance ★ same type
ITGAM c.3060+10dup Uncertain significance ★ same type
ITGAM p.Gln101fs Uncertain significance ★ same type
ITGAM p.Gln1092fs Uncertain significance ★ same type
ITGAM p.Gln437_Asn438insLys Uncertain significance ★ same type
ITGAM p.Gly1086_Ala1087insGlnGly Uncertain significance ★ same type
ITGAM p.Pro1146fs 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-ala423fs (accessed [today's date]).

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