Is ITGA1 p.Pro83Ser (c.247C>T) pathogenic?

ITGA1 p.Pro83Ser (c.247C>T) is classified Uncertain significance in ITGA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-21). AlphaMissense: likely benign (0.129); Ultra-rare (popmax 0.0217%, amr).

How common is ITGA1 p.Pro83Ser (c.247C>T) in the general population?

ITGA1 p.Pro83Ser (c.247C>T) is ultra-rare (popmax 0.0217%, amr) (gnomAD).

What do computational predictors say about ITGA1 p.Pro83Ser (c.247C>T)?

AlphaMissense predicts likely benign (score 0.129) — an in-silico prediction, not a clinical call.

ITGA1 p.Pro83Ser

c.247C>T · VCV3861463

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.129 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0217%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.129	likely benign
REVEL	0.744	pathogenic-leaning
SaProt	LLR -4.44	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	Δ0.21	donor loss · deltas
Constraint at this position
Conservation	phyloP 7.5	GERP 2.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 164 kb · p 0.072 · regional, not allelic
Overall
CADD	25.4	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 0.0217% Admixed American · 13/59,964 alleles

Filtering AF 0.0128% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0101%

Overall 0.00112% 18/1,613,558 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0217%	4,613
Remaining individualsnot grpmax-eligible	0.0016%	62,476
European (non-Finnish)	0.000339%	294,930

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.Pro83Ser
Coding: c.247C>T
MANE Select: NM_181501
Type: single nucleotide variant
Location: chr5:52861511 (GRCh38)
Gene constraint: LOEUF 0.771 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.68 · 7 PDB
Residue 83: a disulfide bond

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

Similar variants

ITGA1 p.Pro83= Benign ★★ same residue
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.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-pro83ser (accessed [today's date]).

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