Is ITGA8 p.Phe758= (c.2274C>T) pathogenic?

ITGA8 p.Phe758= (c.2274C>T) is classified Likely benign in ITGA8 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-08). Very rare (popmax 0.00509%, nfe); Associated with ITGA8-related disorder.

What condition is associated with ITGA8 p.Phe758= (c.2274C>T)?

ITGA8 p.Phe758= (c.2274C>T) is associated with ITGA8-related disorder (ClinVar).

How common is ITGA8 p.Phe758= (c.2274C>T) in the general population?

ITGA8 p.Phe758= (c.2274C>T) is very rare (popmax 0.00509%, nfe) (gnomAD).

ITGA8 p.Phe758=

c.2274C>T · rs764265512 · VCV3050019

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00509%, nfe)

Conditions

ITGA8-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.36	donor loss, 17 bp away · masked 0 · deltas
Pangolin	Δ0.32	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 0.69	GERP 1.1, phastCons 0.96
Overall
CADD	9.086	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00509% European (non-Finnish) · 60/1,179,388 alleles

Filtering AF 0.00402% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00362%

Overall 0.00409% 66/1,613,262 alleles · very rare exomes 64/1,461,068 · genomes 2/152,194 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00509%	19,656
South Asian	0.00439%	22,757
Remaining individualsnot grpmax-eligible	0.0016%	62,464
African / African-American	0.00134%	74,904

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.Phe758=
Coding: c.2274C>T
MANE Select: NM_003638
dbSNP: rs764265512
Type: single nucleotide variant
Location: chr10:15592242 (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.Phe276= 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-phe758 (accessed [today's date]).

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