Is ITGAV p.Val222= (c.666A>G) pathogenic?

ITGAV p.Val222= (c.666A>G) is classified Likely benign in ITGAV (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-06-12). Very rare (popmax 0.00334%, amr); Associated with ITGAV-related disorder.

What condition is associated with ITGAV p.Val222= (c.666A>G)?

ITGAV p.Val222= (c.666A>G) is associated with ITGAV-related disorder (ClinVar).

How common is ITGAV p.Val222= (c.666A>G) in the general population?

ITGAV p.Val222= (c.666A>G) is very rare (popmax 0.00334%, amr) (gnomAD).

ITGAV p.Val222=

c.666A>G · VCV3347183

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Conditions

ITGAV-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.34	phastCons 0.001
Overall
CADD	6.806	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00334% Admixed American · 2/59,948 alleles

Filtering AF 0.000876% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.00031% 5/1,613,354 alleles · very rare exomes 5/1,461,084 · genomes 0/152,270 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,974
South Asian	0.0033%	30,332

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: ITGAV
Protein: p.Val222=
Coding: c.666A>G
MANE Select: NM_002210
Type: single nucleotide variant
Location: chr2:186636116 (GRCh38)
Gene constraint: LOEUF 0.807 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.21 · 59 PDB
Residue 222: an α-helix

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

Disease context

ITGAV-related disorder

Similar variants

ITGAV p.Val222Ile Uncertain significance ★ ⚠ same residue
ITGAV c.903+1G>C Likely pathogenic ★ same condition
ITGAV p.Asp379Val Pathogenic ★ same condition
ITGAV p.Trp144Cys Pathogenic ★ same condition
ITGAV c.2247-1G>A Pathogenic/Likely pathogenic same condition
ITGAV c.802+8G>A Likely benign same condition
ITGAV c.*2T>C Likely benign same condition
ITGAV p.Arg351= 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/itgav-p-val222 (accessed [today's date]).

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