Is ITGAV p.Asp381Asn (c.1141G>A) pathogenic?

ITGAV p.Asp381Asn (c.1141G>A) is classified Uncertain significance in ITGAV (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-29). AlphaMissense: ambiguous (0.3864); Very rare (popmax 0.00254%, nfe).

How common is ITGAV p.Asp381Asn (c.1141G>A) in the general population?

ITGAV p.Asp381Asn (c.1141G>A) is very rare (popmax 0.00254%, nfe) (gnomAD).

What do computational predictors say about ITGAV p.Asp381Asn (c.1141G>A)?

AlphaMissense predicts ambiguous (score 0.3864) — an in-silico prediction, not a clinical call.

ITGAV p.Asp381Asn

c.1141G>A · VCV4088425

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3864 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00254%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3864	ambiguous
REVEL	0.146	moderately benign-leaning
SaProt	LLR -3.65	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.8, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 87 kb · p 0.022 · regional, not allelic
Overall
CADD	23.0	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 0.00254% European (non-Finnish) · 30/1,179,948 alleles

Filtering AF 0.0018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00156%

Overall 0.00186% 30/1,614,032 alleles · very rare exomes 30/1,461,774 · genomes 0/152,258 · joint denominator

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.Asp381Asn
Coding: c.1141G>A
MANE Select: NM_002210
Type: single nucleotide variant
Location: chr2:186641570 (GRCh38)
Gene constraint: LOEUF 0.807 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.21 · 59 PDB
Residue 381: a binding site

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

Similar variants

ITGAV p.Met990Ile Uncertain significance ★★ ⚠ same type
ITGAV p.Ala570= Benign ★★ same type
ITGAV p.Glu147= Benign ★★ same type
ITGAV p.Tyr225= Benign ★★ same type
ITGAV c.1719+1G>A Pathogenic ★ same type
ITGAV c.903+1G>C Likely pathogenic ★ same type
ITGAV p.Asp379Val Pathogenic ★ same type
ITGAV p.Trp144Cys Pathogenic ★ 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/itgav-p-asp381asn (accessed [today's date]).

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