Is ITGA1 p.Arg4Pro (c.11G>C) pathogenic?

ITGA1 p.Arg4Pro (c.11G>C) is classified Uncertain significance in ITGA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-21). AlphaMissense: likely benign (0.1022); Very rare (popmax 0.00123%, sas).

How common is ITGA1 p.Arg4Pro (c.11G>C) in the general population?

ITGA1 p.Arg4Pro (c.11G>C) is very rare (popmax 0.00123%, sas) (gnomAD).

What do computational predictors say about ITGA1 p.Arg4Pro (c.11G>C)?

AlphaMissense predicts likely benign (score 0.1022) — an in-silico prediction, not a clinical call.

ITGA1 p.Arg4Pro

c.11G>C · VCV4277070

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1022 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00123%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1022	likely benign
REVEL	0.113	moderately benign-leaning
SaProt	LLR -6.60	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.32	GERP -4.8
Regional constraint	o/e 0.95	unconstrained · MANE · 164 kb · p 0.072 · regional, not allelic
Overall
CADD	13.64	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 0.00123% South Asian · 1/81,350 alleles

Filtering AF 7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2e-05%

Overall 0.000294% 4/1,358,628 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00123%	81,350
European (non-Finnish)	0.000265%	377,959

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: ITGA1
Protein: p.Arg4Pro
Coding: c.11G>C
Type: single nucleotide variant
Location: chr5:52788364 (GRCh38)

Full ITGA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/itga1-p-arg4pro (accessed [today's date]).

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