Is ITGA3 p.Pro81fs (c.240dup) pathogenic?

ITGA3 p.Pro81fs (c.240dup) is classified Pathogenic/Likely pathogenic in ITGA3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-12). Very rare (popmax 0.00133%, afr); Associated with epidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome.

How common is ITGA3 p.Pro81fs (c.240dup) in the general population?

ITGA3 p.Pro81fs (c.240dup) is very rare (popmax 0.00133%, afr) (gnomAD).

ITGA3 p.Pro81fs

Q: What condition is associated with ITGA3 p.Pro81fs (c.240dup)?

ITGA3 p.Pro81fs (c.240dup) is associated with epidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome (ClinVar).

Q: How is Interstitial lung disease-nephrotic syndrome-epidermolysis bullosa syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.240dup · rs1416855722 · VCV2127941

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

epidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 26
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.9	GERP 0.71, phastCons 0.025

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,980 alleles

Overall 6.2e-05% 1/1,612,770 alleles · very rare exomes 1/1,460,606 · genomes 0/152,164 · 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: ITGA3
Protein: p.Pro81fs
Coding: c.240dup
MANE Select: NM_002204
dbSNP: rs1416855722
Type: Duplication
Location: chr17:50064109 (GRCh38)
Gene constraint: LOEUF 0.69 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.88

Full ITGA3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

epidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Interstitial lung disease-nephrotic syndrome-epidermolysis bullosa syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ITGA3 p.Ala896fs Likely pathogenic ★ same condition
ITGA3 p.Val756fs Likely pathogenic ★ same condition
ITGA3 c.2920-6_2920-1dup Uncertain significance ★ same condition
ITGA3 p.Pro81= Likely benign ★ same residue
ITGA3 c.2070+1G>A Pathogenic ★★ same condition
ITGA3 p.Arg274Gln Likely pathogenic ★★ ⚠ same condition
ITGA3 p.Arg875Ter Likely pathogenic ★★ same condition
ITGA3 c.*48G>A 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/itga3-p-pro81fs (accessed [today's date]).

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