Is ITGA3 p.Arg770Gln (c.2309G>A) pathogenic?

ITGA3 p.Arg770Gln (c.2309G>A) is classified Uncertain significance in ITGA3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-03). AlphaMissense: likely benign (0.0879); Ultra-rare (popmax 0.0661%, mid); Associated with epidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome.

How common is ITGA3 p.Arg770Gln (c.2309G>A) in the general population?

ITGA3 p.Arg770Gln (c.2309G>A) is ultra-rare (popmax 0.0661%, mid) (gnomAD).

What do computational predictors say about ITGA3 p.Arg770Gln (c.2309G>A)?

AlphaMissense predicts likely benign (score 0.0879) — an in-silico prediction, not a clinical call.

ITGA3 p.Arg770Gln

Q: What condition is associated with ITGA3 p.Arg770Gln (c.2309G>A)?

ITGA3 p.Arg770Gln (c.2309G>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.2309G>A · rs149681183 · VCV2181849

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0879 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0661%, mid)

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	0.0879	likely benign
REVEL	0.088	moderately benign-leaning
SaProt	LLR -6.47	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 9.9	GERP -0.25, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 14 kb · p 6.1e-06 · regional, not allelic
Overall
CADD	23.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0661% Middle Eastern · 4/6,052 alleles

Filtering AF 0.0226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0135%

Overall 0.00217% 35/1,609,678 alleles · ultra-rare exomes 26/1,457,492 · genomes 9/152,186 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0661%	1,513
Admixed American	0.00834%	11,996
East Asian	0.00669%	14,953
South Asian	0.0055%	18,193
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,578
African / African-American	0.00267%	37,455
Remaining individualsnot grpmax-eligible	0.0016%	62,386
European (non-Finnish)	0.00119%	84,001

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.Arg770Gln
Coding: c.2309G>A
MANE Select: NM_002204
dbSNP: rs149681183
Type: single nucleotide variant
Location: chr17:50078835 (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.Arg770Trp Conflicting classifications of pathogenicity ★ ⚠ 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-arg770gln (accessed [today's date]).

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