Is ITGB4 p.Cys61Tyr (c.182G>A) pathogenic?

ITGB4 p.Cys61Tyr (c.182G>A) is classified Pathogenic/Likely pathogenic in ITGB4 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2023-12-05). AlphaMissense: likely pathogenic (0.9857); Very rare (popmax 0.005%, amr); Associated with epidermolysis bullosa, junctional 5A, intermediate.

What condition is associated with ITGB4 p.Cys61Tyr (c.182G>A)?

ITGB4 p.Cys61Tyr (c.182G>A) is associated with epidermolysis bullosa, junctional 5A, intermediate, junctional epidermolysis bullosa with pyloric atresia (ClinVar).

How common is ITGB4 p.Cys61Tyr (c.182G>A) in the general population?

ITGB4 p.Cys61Tyr (c.182G>A) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about ITGB4 p.Cys61Tyr (c.182G>A)?

AlphaMissense predicts likely pathogenic (score 0.9857) — an in-silico prediction, not a clinical call.

ITGB4 p.Cys61Tyr

c.182G>A · rs80338755 · VCV14734

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely pathogenic

0.9857 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

epidermolysis bullosa, junctional 5A, intermediate

Computational evidence

Protein change
AlphaMissense	0.9857	likely pathogenic ✓ concordant with ClinVar · top 5% in ITGB4
REVEL	0.964	strongly pathogenic-leaning
SaProt	LLR -14.60	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 33 kb · p 1e-07 · regional, not allelic
Overall
CADD	27.4	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 0.005% Admixed American · 3/60,024 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.00136% 22/1,614,052 alleles · very rare exomes 20/1,461,682 · genomes 2/152,370 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,008
Remaining individualsnot grpmax-eligible	0.0016%	62,506
European (non-Finnish)	0.00153%	65,557

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.Cys61Tyr
Coding: c.182G>A
MANE Select: NM_000213
dbSNP: rs80338755
Type: single nucleotide variant
Location: chr17:75727423 (GRCh38)
Gene constraint: LOEUF 0.86 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.04 · 13 PDB
Residue 61: the psi domain; a disulfide bond; a UniProt-annotated variant site (in jeb5b)

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-cys61tyr (accessed [today's date]).

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