Is ITGA3 p.Ala74= (c.222C>T) pathogenic?

ITGA3 p.Ala74= (c.222C>T) is classified Benign/Likely benign in ITGA3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-19). Rare (popmax 0.303%, eas); Associated with epidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome.

How common is ITGA3 p.Ala74= (c.222C>T) in the general population?

ITGA3 p.Ala74= (c.222C>T) is rare (popmax 0.303%, eas) (gnomAD).

ITGA3 p.Ala74=

Q: What condition is associated with ITGA3 p.Ala74= (c.222C>T)?

ITGA3 p.Ala74= (c.222C>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.222C>T · rs201984415 · VCV732306

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.303%, eas)

Conditions

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

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.15	GERP -1.8, phastCons 0.5
Overall
CADD	10.76	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.303% East Asian · 136/44,850 alleles

Filtering AF 0.262% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.246%

Overall 0.0115% 186/1,612,726 alleles · rare exomes 162/1,460,620 · genomes 24/152,106 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.303%	330
Remaining individualsnot grpmax-eligible	0.0449%	2,230
South Asian	0.0176%	5,670
Admixed American	0.00167%	59,916
African / African-American	0.00133%	74,956
European (non-Finnish)	0.000339%	294,932

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.Ala74=
Coding: c.222C>T
MANE Select: NM_002204
dbSNP: rs201984415
Type: single nucleotide variant
Location: chr17:50064092 (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-ala74 (accessed [today's date]).

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