Is ITGAV p.Pro606Ser (c.1816C>T) pathogenic?

ITGAV p.Pro606Ser (c.1816C>T) is classified Uncertain significance in ITGAV (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: likely pathogenic (0.9431); Ultra-rare (popmax 0.0164%, mid).

How common is ITGAV p.Pro606Ser (c.1816C>T) in the general population?

ITGAV p.Pro606Ser (c.1816C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about ITGAV p.Pro606Ser (c.1816C>T)?

AlphaMissense predicts likely pathogenic (score 0.9431) — an in-silico prediction, not a clinical call.

ITGAV p.Pro606Ser

c.1816C>T · VCV4679933

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9431 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9431	likely pathogenic
REVEL	0.7	pathogenic-leaning
SaProt	LLR -11.09	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 87 kb · p 0.022 · regional, not allelic
Overall
CADD	26.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0164% Middle Eastern · 1/6,080 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00105% 17/1,612,844 alleles · ultra-rare exomes 16/1,460,772 · genomes 1/152,072 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,080
European (non-Finnish)	0.00136%	73,700

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.Pro606Ser
Coding: c.1816C>T
MANE Select: NM_002210
Type: single nucleotide variant
Location: chr2:186659134 (GRCh38)
Gene constraint: LOEUF 0.807 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.21 · 59 PDB
Residue 606: an α-helix

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-pro606ser (accessed [today's date]).

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