Is ITGB4 p.Ser607= (c.1821G>A) pathogenic?

ITGB4 p.Ser607= (c.1821G>A) is classified Benign/Likely benign in ITGB4 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-03). Common (popmax 37.4%, eas) — too common for a highly-penetrant pathogenic allele; Associated with junctional epidermolysis bullosa with pyloric atresia.

What condition is associated with ITGB4 p.Ser607= (c.1821G>A)?

ITGB4 p.Ser607= (c.1821G>A) is associated with junctional epidermolysis bullosa with pyloric atresia (ClinVar).

ITGB4 p.Ser607=

Q: How common is ITGB4 p.Ser607= (c.1821G>A) in the general population?

ITGB4 p.Ser607= (c.1821G>A) is common (popmax 37.4%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

Q: How is Junctional epidermolysis bullosa with pyloric atresia inherited?

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

c.1821G>A · rs2290460 · VCV325151

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 37.4%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

junctional epidermolysis bullosa with pyloric atresia

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 -13
Overall
CADD	1.456	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 37.4% East Asian · 16,798/44,858 alleles

Filtering AF 37% ClinGen BA1/BS1 input FAF95, joint · FAF99 36.8%

Overall 4.3% 69,369/1,613,996 alleles · common exomes 59,996/1,461,802 · genomes 9,373/152,194 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	37.4%	3
Admixed American	20.5%	5
South Asian	18.5%	5
African / African-American	7.83%	13
Remaining individualsnot grpmax-eligible	5.15%	19
Finnishnot grpmax-eligible	3.44%	29
Middle Eastern	2.87%	35
Ashkenazi Jewishnot grpmax-eligible	2.49%	40
European (non-Finnish)	0.949%	105

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.Ser607=
Coding: c.1821G>A
MANE Select: NM_000213
dbSNP: rs2290460
Type: single nucleotide variant
Location: chr17:75736347 (GRCh38)
Gene constraint: LOEUF 0.86 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.04 · 13 PDB
Residue 607: the i-egf 4 domain

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

Disease context

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

For Junctional epidermolysis bullosa with pyloric atresia (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Neonatal

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-ser607 (accessed [today's date]).

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