Is ITGA1 p.Pro153Arg (c.458C>G) pathogenic?

ITGA1 p.Pro153Arg (c.458C>G) is classified Uncertain significance in ITGA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-30). AlphaMissense: likely benign (0.103); Absent from gnomAD v4.1.

How common is ITGA1 p.Pro153Arg (c.458C>G) in the general population?

ITGA1 p.Pro153Arg (c.458C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ITGA1 p.Pro153Arg (c.458C>G)?

AlphaMissense predicts likely benign (score 0.103) — an in-silico prediction, not a clinical call.

ITGA1 p.Pro153Arg

c.458C>G · VCV3286667

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.103 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.103	likely benign
REVEL	0.215	benign-leaning
SaProt	LLR -7.36	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 164 kb · p 0.072 · regional, not allelic
Overall
CADD	26.3	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ITGA1
Protein: p.Pro153Arg
Coding: c.458C>G
MANE Select: NM_181501
Type: single nucleotide variant
Location: chr5:52865044 (GRCh38)
Gene constraint: LOEUF 0.771 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.68 · 7 PDB

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

Similar variants

ITGA1 p.Ala823Thr Uncertain significance ★★ ⚠ same type
ITGA1 p.Asn966Ser Uncertain significance ★★ ⚠ same type
ITGA1 c.1455+7T>C Benign ★★ same type
ITGA1 p.Glu221= Benign ★★ same type
ITGA1 p.Phe737= Benign ★★ same type
ITGA1 p.Pro83= Benign ★★ same type
ITGA1 p.Ser1096= Benign ★★ same type
ITGA1 p.Ser1121Arg Benign ★★ 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/itga1-p-pro153arg (accessed [today's date]).

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