Is ITGA4 p.Val28Ile (c.82G>A) pathogenic?

ITGA4 p.Val28Ile (c.82G>A) is classified Uncertain significance in ITGA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-02). AlphaMissense: likely benign (0.0673); Ultra-rare (popmax 0.0293%, afr).

How common is ITGA4 p.Val28Ile (c.82G>A) in the general population?

ITGA4 p.Val28Ile (c.82G>A) is ultra-rare (popmax 0.0293%, afr) (gnomAD).

What do computational predictors say about ITGA4 p.Val28Ile (c.82G>A)?

AlphaMissense predicts likely benign (score 0.0673) — an in-silico prediction, not a clinical call.

ITGA4 p.Val28Ile

c.82G>A · rs202188020 · VCV3111238

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0673 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0293%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0673	likely benign
REVEL	0.142	moderately benign-leaning
SaProt	LLR -7.33	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.018	GERP -3, phastCons 0.001
Regional constraint	o/e 1.20	unconstrained · MANE · 145 bp · p 0.097 · regional, not allelic
Overall
CADD	9.261	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0293% African / African-American · 22/74,974 alleles

Filtering AF 0.0198% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0167%

Overall 0.00161% 26/1,612,950 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0293%	3,408
Middle Eastern	0.0166%	6,032
Remaining individualsnot grpmax-eligible	0.0016%	62,432
Finnishnot grpmax-eligible	0.00157%	63,496
European (non-Finnish)	8.48e-05%	1,179,786

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: ITGA4
Protein: p.Val28Ile
Coding: c.82G>A
MANE Select: NM_000885
dbSNP: rs202188020
Type: single nucleotide variant
Location: chr2:181457736 (GRCh38)
Gene constraint: LOEUF 0.603 · pLI 0.20 (gnomAD)
Structure: AlphaFold pLDDT 84.11 · 7 PDB

Full ITGA4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ITGA4 p.Val28Phe Uncertain significance ★ ⚠ same residue
ITGA4 c.1042-6A>G Benign ★★ same type
ITGA4 c.2884-7C>G Likely benign ★★ same type
ITGA4 c.754+10A>C Benign ★★ same type
ITGA4 c.841-15T>C Benign ★★ same type
ITGA4 p.Ser634Thr Benign ★★ same type
ITGA4 c.*2719T>C Likely pathogenic ★ same type
CERKL c.*1212A>G 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/itga4-p-val28ile (accessed [today's date]).

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