Is GJA3 p.Phe77= (c.231C>T) pathogenic?

GJA3 p.Phe77= (c.231C>T) is classified Benign in GJA3 (ClinVar, Single submitter, 2 submitters; last evaluated 2018-01-13). Ultra-rare (popmax 0.0333%, nfe); Associated with cataract 14 multiple types.

What condition is associated with GJA3 p.Phe77= (c.231C>T)?

GJA3 p.Phe77= (c.231C>T) is associated with cataract 14 multiple types (ClinVar).

How common is GJA3 p.Phe77= (c.231C>T) in the general population?

GJA3 p.Phe77= (c.231C>T) is ultra-rare (popmax 0.0333%, nfe) (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.Phe77=

c.231C>T · rs143508620 · VCV311348

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0333%, nfe)

Conditions

cataract 14 multiple types

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.7	GERP 1.9, phastCons 1
Overall
CADD	11.32	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0333% European (non-Finnish) · 393/1,179,888 alleles

Filtering AF 0.0305% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0294%

Overall 0.143% 2,311/1,613,844 alleles · ultra-rare exomes 1,915/1,461,494 · genomes 396/152,350 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	2.86%	35
Remaining individualsnot grpmax-eligible	0.122%	822
European (non-Finnish)grpmax	0.0333%	3,002
Middle Eastern	0.033%	3,031
East Asian	0.00669%	14,956
Admixed American	0.005%	19,983
South Asian	0.0033%	30,341
African / African-American	0.00266%	37,528

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Phe77=
Coding: c.231C>T
MANE Select: NM_021954
dbSNP: rs143508620
Type: single nucleotide variant
Location: chr13:20143058 (GRCh38)
Gene constraint: LOEUF 1.922 · pLI 0.13 (gnomAD)
Structure: AlphaFold pLDDT 69.53

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.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
GJA3 p.Glu62Lys Pathogenic/Likely pathogenic ★★ ⚠ same condition
GJA3 p.Gly143Arg Pathogenic/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-phe77 (accessed [today's date]).

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