Is ITGB4 p.Pro129= (c.387C>T) pathogenic?

ITGB4 p.Pro129= (c.387C>T) is classified Likely benign in ITGB4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-12). Rare (popmax 0.139%, afr); Associated with epidermolysis bullosa, junctional 5A, intermediate.

What condition is associated with ITGB4 p.Pro129= (c.387C>T)?

ITGB4 p.Pro129= (c.387C>T) is associated with epidermolysis bullosa, junctional 5A, intermediate, junctional epidermolysis bullosa with pyloric atresia (ClinVar).

How common is ITGB4 p.Pro129= (c.387C>T) in the general population?

ITGB4 p.Pro129= (c.387C>T) is rare (popmax 0.139%, afr) (gnomAD).

ITGB4 p.Pro129=

c.387C>T · rs140040189 · VCV715088

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.139%, afr)

Conditions

epidermolysis bullosa, junctional 5A, intermediate

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7
Overall
CADD	7.962	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.139% African / African-American · 104/75,040 alleles

Filtering AF 0.117% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.109%

Overall 0.00886% 143/1,614,066 alleles · rare exomes 73/1,461,784 · genomes 70/152,282 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.139%	722
Admixed American	0.0417%	2,401
Remaining individualsnot grpmax-eligible	0.0048%	20,832
South Asian	0.0022%	45,534
Finnishnot grpmax-eligible	0.00156%	64,032
European (non-Finnish)	0.000678%	147,498

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: ITGB4
Protein: p.Pro129=
Coding: c.387C>T
MANE Select: NM_000213
dbSNP: rs140040189
Type: single nucleotide variant
Location: chr17:75727773 (GRCh38)
Gene constraint: LOEUF 0.86 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.04 · 13 PDB

Full ITGB4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

epidermolysis bullosa, junctional 5A, intermediate — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: junctional epidermolysis bullosa with pyloric atresia

Similar variants

ITGB4 c.2254+1G>T Pathogenic/Likely pathogenic ★★ same condition
ITGB4 c.2550+1G>A Pathogenic/Likely pathogenic ★★ same condition
ITGB4 c.2633+1G>A Pathogenic/Likely pathogenic ★★ same condition
ITGB4 c.2783-2A>G Pathogenic/Likely pathogenic ★★ same condition
ITGB4 c.3793+1G>A Pathogenic ★★ same condition
ITGB4 p.Ala620= Pathogenic/Likely pathogenic ★★ same condition
ITGB4 p.Arg1225His Pathogenic/Likely pathogenic ★★ ⚠ same condition
ITGB4 p.Arg252Cys Pathogenic/Likely pathogenic ★★ 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/itgb4-p-pro129 (accessed [today's date]).

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