Is ITGAV p.Pro1027Arg (c.3080C>G) pathogenic?

ITGAV p.Pro1027Arg (c.3080C>G) is classified Uncertain significance in ITGAV (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-20). AlphaMissense: likely pathogenic (0.8297); Very rare (popmax 0.000424%, nfe).

How common is ITGAV p.Pro1027Arg (c.3080C>G) in the general population?

ITGAV p.Pro1027Arg (c.3080C>G) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about ITGAV p.Pro1027Arg (c.3080C>G)?

AlphaMissense predicts likely pathogenic (score 0.8297) — an in-silico prediction, not a clinical call.

ITGAV p.Pro1027Arg

c.3080C>G · VCV3530521

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8297 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8297	likely pathogenic
REVEL	0.643	indeterminate
SaProt	LLR -6.83	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 87 kb · p 0.022 · regional, not allelic
Overall
CADD	27.8	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 0.000424% European (non-Finnish) · 5/1,179,798 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000342% 5/1,461,512 alleles · very rare

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.Pro1027Arg
Coding: c.3080C>G
MANE Select: NM_002210
Type: single nucleotide variant
Location: chr2:186677225 (GRCh38)
Gene constraint: LOEUF 0.807 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.21 · 59 PDB
Residue 1027: the 'disordered' region

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-pro1027arg (accessed [today's date]).

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