Is ITGA3 p.Val838Ile (c.2512G>A) pathogenic?

ITGA3 p.Val838Ile (c.2512G>A) is classified Conflicting classifications of pathogenicity in ITGA3 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-08-19). AlphaMissense: likely benign (0.0661); Ultra-rare (popmax 0.0167%, amr); Associated with epidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome.

How common is ITGA3 p.Val838Ile (c.2512G>A) in the general population?

ITGA3 p.Val838Ile (c.2512G>A) is ultra-rare (popmax 0.0167%, amr) (gnomAD).

What do computational predictors say about ITGA3 p.Val838Ile (c.2512G>A)?

AlphaMissense predicts likely benign (score 0.0661) — an in-silico prediction, not a clinical call.

ITGA3 p.Val838Ile

Q: What condition is associated with ITGA3 p.Val838Ile (c.2512G>A)?

ITGA3 p.Val838Ile (c.2512G>A) 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.2512G>A · rs370218357 · VCV2070073

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0661 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

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

Computational evidence

Protein change
AlphaMissense	0.0661	likely benign
REVEL	0.211	benign-leaning
SaProt	LLR -6.82	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.81	GERP -3.9
Regional constraint	o/e 0.84	unconstrained · MANE · 14 kb · p 6.1e-06 · regional, not allelic
Overall
CADD	0.102	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 0.0167% Admixed American · 10/60,006 alleles

Filtering AF 0.009% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00681%

Overall 0.00341% 55/1,613,930 alleles · ultra-rare exomes 52/1,461,790 · genomes 3/152,140 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0167%	6,001
Middle Eastern	0.0165%	6,062
East Asian	0.0156%	6,409
African / African-American	0.00667%	14,995
Remaining individualsnot grpmax-eligible	0.0048%	20,833
European (non-Finnish)	0.00229%	43,700
South Asian	0.0022%	45,542

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.Val838Ile
Coding: c.2512G>A
MANE Select: NM_002204
dbSNP: rs370218357
Type: single nucleotide variant
Location: chr17:50079187 (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 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
ITGA3 p.Arg156Trp 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-val838ile (accessed [today's date]).

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