Is ITGB6 p.Ser53Pro (c.157T>C) pathogenic?

ITGB6 p.Ser53Pro (c.157T>C) is classified Uncertain significance in ITGB6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-27). AlphaMissense: likely benign (0.1318); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with ITGB6 p.Ser53Pro (c.157T>C)?

ITGB6 p.Ser53Pro (c.157T>C) is associated with Inborn genetic diseases (ClinVar).

How common is ITGB6 p.Ser53Pro (c.157T>C) in the general population?

ITGB6 p.Ser53Pro (c.157T>C) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about ITGB6 p.Ser53Pro (c.157T>C)?

AlphaMissense predicts likely benign (score 0.1318) — an in-silico prediction, not a clinical call.

ITGB6 p.Ser53Pro

c.157T>C · rs761037603 · VCV3111496

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1318 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1318	likely benign
REVEL	0.214	benign-leaning
SaProt	LLR -8.45	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 5.5	GERP 1.3, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 98 kb · p 0.22 · regional, not allelic
Overall
CADD	18.29	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 0.00223% East Asian · 1/44,870 alleles

Filtering AF 0.00146% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00161% 26/1,609,908 alleles · very rare exomes 23/1,457,704 · genomes 3/152,204 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,870
European (non-Finnish)	0.00212%	47,138

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: ITGB6
Protein: p.Ser53Pro
Coding: c.157T>C
MANE Select: NM_000888
dbSNP: rs761037603
Type: single nucleotide variant
Location: chr2:160196405 (GRCh38)
Gene constraint: LOEUF 1.196 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.96 · 14 PDB
Residue 53: the psi domain

Full ITGB6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ITGB6 p.Ala342Thr Uncertain significance ★★ ⚠ same condition
ITGB6 p.Glu333Gly Uncertain significance ★★ ⚠ same condition
ITGB6 p.Ile694Phe Uncertain significance ★★ ⚠ same condition
ITGB6 p.Val419Leu Uncertain significance ★★ ⚠ same condition
ITGB6 p.Ala234Val Uncertain significance ★ ⚠ same condition
ITGB6 p.Ala245Thr Uncertain significance ★ ⚠ same condition
ITGB6 p.Ala250Thr Uncertain significance ★ ⚠ same condition
ITGB6 p.Ala367Pro Uncertain significance ★ ⚠ same condition

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/itgb6-p-ser53pro (accessed [today's date]).

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