Is ITGA6 p.Pro67= (c.201G>A) pathogenic?

ITGA6 p.Pro67= (c.201G>A) is classified Likely benign in ITGA6 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-06-12). Ultra-rare (popmax 0.0986%, afr); Associated with epidermolysis bullosa, junctional 6, with pyloric atresia.

What condition is associated with ITGA6 p.Pro67= (c.201G>A)?

ITGA6 p.Pro67= (c.201G>A) is associated with epidermolysis bullosa, junctional 6, with pyloric atresia (ClinVar).

How common is ITGA6 p.Pro67= (c.201G>A) in the general population?

ITGA6 p.Pro67= (c.201G>A) is ultra-rare (popmax 0.0986%, afr) (gnomAD).

ITGA6 p.Pro67=

c.201G>A · rs143545213 · VCV745028

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0986%, afr)

Conditions

epidermolysis bullosa, junctional 6, with pyloric atresia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.5	GERP -3.8
Overall
CADD	5.51	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0986% African / African-American · 74/75,060 alleles

Filtering AF 0.0805% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0738%

Overall 0.00712% 115/1,614,192 alleles · ultra-rare exomes 65/1,461,850 · genomes 50/152,342 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0986%	1,014
Remaining individualsnot grpmax-eligible	0.0256%	3,907
Admixed American	0.00833%	12,006
South Asian	0.0022%	45,542
European (non-Finnish)	0.00153%	65,558

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: ITGA6
Protein: p.Pro67=
Coding: c.201G>A
MANE Select: NM_000210
dbSNP: rs143545213
Type: single nucleotide variant
Location: chr2:172465557 (GRCh38)
Gene constraint: LOEUF 0.52 · pLI 0.69 (gnomAD)
Structure: AlphaFold pLDDT 80.05 · 2 PDB

Full ITGA6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

epidermolysis bullosa, junctional 6, with pyloric atresia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ITGA6 p.Arg148Ter Pathogenic/Likely pathogenic ★★ same condition
ITGA6 p.Arg976Ter Pathogenic/Likely pathogenic ★★ same condition
ITGA6 c.986+3G>A Uncertain significance ★★ same condition
ITGA6 c.*65C>G Uncertain significance ★★ ⚠ same condition
ITGA6 p.Ala1024Thr Uncertain significance ★★ ⚠ same condition
ITGA6 p.Ala321Val Uncertain significance ★★ ⚠ same condition
ITGA6 p.Arg19Trp Uncertain significance ★★ ⚠ same condition
ITGA6 p.Arg484Cys 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/itga6-p-pro67 (accessed [today's date]).

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