Is ITGA3 p.Arg276Ter (c.826C>T) pathogenic?

ITGA3 p.Arg276Ter (c.826C>T) is classified Likely pathogenic in ITGA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-09). Very rare (popmax 0.00223%, eas); Associated with ITGA3-related disorder.

What condition is associated with ITGA3 p.Arg276Ter (c.826C>T)?

ITGA3 p.Arg276Ter (c.826C>T) is associated with ITGA3-related disorder (ClinVar).

How common is ITGA3 p.Arg276Ter (c.826C>T) in the general population?

ITGA3 p.Arg276Ter (c.826C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

ITGA3 p.Arg276Ter

c.826C>T · rs777480064 · VCV2631652

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 0.00223%, eas)

Conditions

ITGA3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 26
Splicing
SpliceAI	Δ0.42	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 2.7	GERP 0.82, phastCons 0.99
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 0.00223% East Asian · 1/44,882 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000248% 4/1,614,172 alleles · very rare exomes 4/1,461,838 · genomes 0/152,334 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,882
Remaining individualsnot grpmax-eligible	0.0016%	62,512
European (non-Finnish)	0.000169%	590,019

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.Arg276Ter
Coding: c.826C>T
MANE Select: NM_002204
dbSNP: rs777480064
Type: single nucleotide variant
Location: chr17:50071385 (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 disorder

Similar variants

ITGA3 p.Arg276Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
ITGA3 p.Arg932Ter Likely pathogenic ★ same condition
ITGA3 p.Gln348Ter 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

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-arg276ter (accessed [today's date]).

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