Is ITGA8 p.Phe276= (c.828T>C) pathogenic?

ITGA8 p.Phe276= (c.828T>C) is classified Likely benign in ITGA8 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-12-17). Ultra-rare (popmax 0.0156%, eas); Associated with ITGA8-related disorder.

What condition is associated with ITGA8 p.Phe276= (c.828T>C)?

ITGA8 p.Phe276= (c.828T>C) is associated with ITGA8-related disorder (ClinVar).

How common is ITGA8 p.Phe276= (c.828T>C) in the general population?

ITGA8 p.Phe276= (c.828T>C) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

ITGA8 p.Phe276=

c.828T>C · rs750078964 · VCV3045881

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Conditions

ITGA8-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2	GERP -3.7, phastCons 1
Overall
CADD	5.458	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0156% East Asian · 7/44,832 alleles

Filtering AF 0.00727% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.00093% 15/1,612,926 alleles · ultra-rare exomes 15/1,460,644 · genomes 0/152,282 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,405
Remaining individualsnot grpmax-eligible	0.0048%	20,821
South Asian	0.00439%	22,759
European (non-Finnish)	8.48e-05%	1,179,030

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: ITGA8
Protein: p.Phe276=
Coding: c.828T>C
MANE Select: NM_003638
dbSNP: rs750078964
Type: single nucleotide variant
Location: chr10:15671622 (GRCh38)
Gene constraint: LOEUF 0.801 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.08

Full ITGA8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ITGA8-related disorder

Similar variants

ITGA8 p.Gln876Ter Likely pathogenic ★★ same condition
ITGA8 p.Arg952Ter Pathogenic ★ same condition
ITGA8 p.Met498Leu Uncertain significance ★ ⚠ same condition
ITGA8 p.Arg594Ter Pathogenic same condition
ITGA8 p.Tyr56Ter Uncertain significance same condition
ITGA8 c.2638-6T>G Likely benign same condition
ITGA8 p.Arg7= Likely benign same condition
ITGA8 p.Phe57= 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/itga8-p-phe276 (accessed [today's date]).

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