Is ITGB6 p.Ser671Pro (c.2011T>C) pathogenic?

ITGB6 p.Ser671Pro (c.2011T>C) is classified Uncertain significance in ITGB6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-28). AlphaMissense: ambiguous (0.3479); Very rare (popmax 0.00119%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ITGB6 p.Ser671Pro (c.2011T>C)?

ITGB6 p.Ser671Pro (c.2011T>C) is associated with Inborn genetic diseases (ClinVar).

How common is ITGB6 p.Ser671Pro (c.2011T>C) in the general population?

ITGB6 p.Ser671Pro (c.2011T>C) is very rare (popmax 0.00119%, nfe) (gnomAD).

What do computational predictors say about ITGB6 p.Ser671Pro (c.2011T>C)?

AlphaMissense predicts ambiguous (score 0.3479) — an in-silico prediction, not a clinical call.

ITGB6 p.Ser671Pro

c.2011T>C · VCV4622326

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3479 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00119%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3479	ambiguous
REVEL	0.568	indeterminate
SaProt	LLR -14.85	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.1	GERP 2.4, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 98 kb · p 0.22 · regional, not allelic
Overall
CADD	24.7	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 0.00119% European (non-Finnish) · 14/1,178,738 alleles

Filtering AF 0.000689% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.000868% 14/1,612,534 alleles · very rare exomes 14/1,460,210 · genomes 0/152,324 · joint denominator

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.Ser671Pro
Coding: c.2011T>C
MANE Select: NM_000888
Type: single nucleotide variant
Location: chr2:160112170 (GRCh38)
Gene constraint: LOEUF 1.196 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.96 · 14 PDB

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-ser671pro (accessed [today's date]).

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