Is ITGA3 p.Gln348Ter (c.1042C>T) pathogenic?

ITGA3 p.Gln348Ter (c.1042C>T) is classified Likely pathogenic in ITGA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-22). Very rare (popmax 0.000508%, nfe); Associated with ITGA3-related disorders.

What condition is associated with ITGA3 p.Gln348Ter (c.1042C>T)?

ITGA3 p.Gln348Ter (c.1042C>T) is associated with ITGA3-related disorders (ClinVar).

How common is ITGA3 p.Gln348Ter (c.1042C>T) in the general population?

ITGA3 p.Gln348Ter (c.1042C>T) is very rare (popmax 0.000508%, nfe) (gnomAD).

ITGA3 p.Gln348Ter

c.1042C>T · VCV4935789

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000508%, nfe)

Conditions

ITGA3-related disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 26
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.8	GERP 2.1, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000508% European (non-Finnish) · 6/1,180,020 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,613,974 alleles · very rare exomes 3/1,461,862 · genomes 3/152,112 · joint denominator

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: ITGA3
Protein: p.Gln348Ter
Coding: c.1042C>T
MANE Select: NM_002204
Type: single nucleotide variant
Location: chr17:50072068 (GRCh38)
Gene constraint: LOEUF 0.69 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.88

Full ITGA3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ITGA3-related disorders

Similar variants

ITGA3 p.Arg276Ter Likely pathogenic ★ same condition
ITGA3 p.Arg932Ter Likely pathogenic ★ same condition
ITGA3 p.Asp36Tyr Uncertain significance ★ ⚠ same condition
ITGA3 p.Pro506Thr Uncertain significance ⚠ same condition
ITGA3 c.1537+8C>A Likely benign same condition
ITGA3 c.2706+9C>T Likely benign same condition
ITGA3 p.Ala312= Likely benign same condition
ITGA3 p.Arg295= Likely benign same condition

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/itga3-p-gln348ter (accessed [today's date]).

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