Is ITGA3 p.Ser645Ile (c.1934G>T) pathogenic?

ITGA3 p.Ser645Ile (c.1934G>T) is classified Uncertain significance in ITGA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-21). AlphaMissense: ambiguous (0.3786); Absent from gnomAD v4.1; Associated with epidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome.

How common is ITGA3 p.Ser645Ile (c.1934G>T) in the general population?

ITGA3 p.Ser645Ile (c.1934G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ITGA3 p.Ser645Ile (c.1934G>T)?

AlphaMissense predicts ambiguous (score 0.3786) — an in-silico prediction, not a clinical call.

ITGA3 p.Ser645Ile

Q: What condition is associated with ITGA3 p.Ser645Ile (c.1934G>T)?

ITGA3 p.Ser645Ile (c.1934G>T) 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.1934G>T · VCV3582267

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3786 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

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

Computational evidence

Protein change
AlphaMissense	0.3786	ambiguous
REVEL	0.118	moderately benign-leaning
SaProt	LLR -8.75	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 0.88, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 14 kb · p 6.1e-06 · regional, not allelic
Overall
CADD	25.3	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ITGA3
Protein: p.Ser645Ile
Coding: c.1934G>T
MANE Select: NM_002204
Type: single nucleotide variant
Location: chr17:50076985 (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.Ser645Cys Uncertain significance ★ 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
ITGA3 c.*96G>A Uncertain significance ★★ same condition
ITGA3 p.Ala1026Val Uncertain significance ★★ ⚠ same condition
ITGA3 p.Ala1035Val 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-ser645ile (accessed [today's date]).

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