Is ITGA8 p.Val73Phe (c.217G>T) pathogenic?

ITGA8 p.Val73Phe (c.217G>T) is classified Uncertain significance in ITGA8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-25). AlphaMissense: ambiguous (0.4322); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ITGA8 p.Val73Phe (c.217G>T)?

ITGA8 p.Val73Phe (c.217G>T) is associated with Inborn genetic diseases (ClinVar).

How common is ITGA8 p.Val73Phe (c.217G>T) in the general population?

ITGA8 p.Val73Phe (c.217G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ITGA8 p.Val73Phe (c.217G>T)?

AlphaMissense predicts ambiguous (score 0.4322) — an in-silico prediction, not a clinical call.

ITGA8 p.Val73Phe

c.217G>T · VCV3530432

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4322 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4322	ambiguous
REVEL	0.764	pathogenic-leaning
SaProt	LLR -8.02	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP -0.69, phastCons 0.99
Regional constraint	o/e 1.06	unconstrained · MANE · 203 kb · p 0.032 · regional, not allelic
Overall
CADD	26.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ITGA8
Protein: p.Val73Phe
Coding: c.217G>T
MANE Select: NM_003638
Type: single nucleotide variant
Location: chr10:15718892 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ITGA8 p.Ala848Ser Uncertain significance ★★ ⚠ same condition
ITGA8 p.Arg588Gln Uncertain significance ★★ ⚠ same condition
ITGA8 p.Asn40Thr Uncertain significance ★★ ⚠ same condition
ITGA8 p.Glu815Asp Uncertain significance ★★ ⚠ same condition
ITGA8 p.Gly387Ser Uncertain significance ★★ ⚠ same condition
ITGA8 p.Gly449Arg Uncertain significance ★★ ⚠ same condition
ITGA8 p.His392Arg Uncertain significance ★★ ⚠ same condition
ITGA8 p.Ile637Met Uncertain significance ★★ ⚠ 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-val73phe (accessed [today's date]).

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