Is ITGA8 p.Val799Phe (c.2395G>T) pathogenic?

ITGA8 p.Val799Phe (c.2395G>T) is classified Likely benign in ITGA8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-16). AlphaMissense: likely benign (0.2678); Rare (popmax 0.689%, eas).

How common is ITGA8 p.Val799Phe (c.2395G>T) in the general population?

ITGA8 p.Val799Phe (c.2395G>T) is rare (popmax 0.689%, eas) (gnomAD).

What do computational predictors say about ITGA8 p.Val799Phe (c.2395G>T)?

AlphaMissense predicts likely benign (score 0.2678) — an in-silico prediction, not a clinical call.

ITGA8 p.Val799Phe

c.2395G>T · VCV3667182

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2678 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.689%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2678	likely benign
REVEL	0.214	benign-leaning
SaProt	LLR -4.20	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.8	GERP -0.008, phastCons 0.33
Regional constraint	o/e 1.06	unconstrained · MANE · 203 kb · p 0.032 · regional, not allelic
Overall
CADD	15.82	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

Grpmax group 0.689% East Asian · 309/44,862 alleles

Filtering AF 0.626% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.601%

Overall 0.033% 533/1,613,840 alleles · rare exomes 487/1,461,548 · genomes 46/152,292 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.689%	145
Remaining individualsnot grpmax-eligible	0.0464%	2,155
Middle Eastern	0.0165%	6,058
Finnishnot grpmax-eligible	0.0156%	6,401
South Asian	0.0154%	6,505
European (non-Finnish)	0.0137%	7,283
African / African-American	0.00666%	15,007
Admixed American	0.005%	20,005

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.Val799Phe
Coding: c.2395G>T
MANE Select: NM_003638
Type: single nucleotide variant
Location: chr10:15575572 (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

Similar variants

ITGA8 c.2982+2T>C Pathogenic/Likely pathogenic ★★ same type
ITGA8 p.Arg938Ter Pathogenic ★★ same type
ITGA8 p.Gln876Ter Likely pathogenic ★★ same type
ITGA8 p.Ala552Thr Uncertain significance ★★ ⚠ same type
ITGA8 p.Ala848Ser Uncertain significance ★★ ⚠ same type
ITGA8 p.Arg588Gln Uncertain significance ★★ ⚠ same type
ITGA8 p.Asn40Thr Uncertain significance ★★ ⚠ same type
ITGA8 p.Glu815Asp Uncertain significance ★★ ⚠ same type

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-val799phe (accessed [today's date]).

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