Is GJA3 p.Val28= (c.84G>A) pathogenic?

GJA3 p.Val28= (c.84G>A) is classified Benign/Likely benign in GJA3 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-03-06). Rare (popmax 0.714%, sas); Associated with cataract 14 multiple types.

What condition is associated with GJA3 p.Val28= (c.84G>A)?

GJA3 p.Val28= (c.84G>A) is associated with cataract 14 multiple types (ClinVar).

How common is GJA3 p.Val28= (c.84G>A) in the general population?

GJA3 p.Val28= (c.84G>A) is rare (popmax 0.714%, sas) (gnomAD).

How is Early onset non-syndromic cataract inherited?

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

GJA3 p.Val28=

c.84G>A · rs531379398 · VCV311349

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.714%, sas)

Conditions

cataract 14 multiple types

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 0.61	GERP 0.88, phastCons 1
Overall
CADD	7.898	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.714% South Asian · 606/84,816 alleles

Filtering AF 0.667% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.649%

Overall 0.0398% 630/1,581,858 alleles · rare exomes 603/1,429,490 · genomes 27/152,368 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.714%	140
Middle Eastern	0.0338%	2,956
Remaining individualsnot grpmax-eligible	0.0245%	4,077
African / African-American	0.00268%	37,335
Admixed American	0.00171%	58,418
European (non-Finnish)	0.000344%	290,487

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: GJA3
Protein: p.Val28=
Coding: c.84G>A
MANE Select: NM_021954
dbSNP: rs531379398
Type: single nucleotide variant
Location: chr13:20143205 (GRCh38)
Gene constraint: LOEUF 1.922 · pLI 0.13 (gnomAD)
Structure: AlphaFold pLDDT 69.53
Residue 28: a UniProt-annotated variant site (in ctrct14)

Full GJA3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cataract 14 multiple types — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Early onset non-syndromic cataract (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Infancy, Neonatal

Similar variants

GJA3 p.Val28Leu Uncertain significance ★ ⚠ same residue
GJA3 p.Val28Met Conflicting classifications of pathogenicity ★ ⚠ same residue
GJA3 p.Arg33Leu Likely pathogenic ★★ same condition
GJA3 p.Arg76Cys Pathogenic/Likely pathogenic ★★ same condition
GJA3 p.Arg76His Pathogenic/Likely pathogenic ★★ same condition
GJA3 p.Asp3Tyr Pathogenic/Likely pathogenic ★★ same condition
GJA3 p.Asp47Asn Pathogenic/Likely pathogenic ★★ same condition
GJA3 p.Asp51His 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/gja3-p-val28 (accessed [today's date]).

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