Is GJA5 p.Val85= (c.255C>A) pathogenic?

GJA5 p.Val85= (c.255C>A) is classified Likely benign in GJA5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-02). Very rare (popmax 8.47e-05%, nfe); Associated with atrial fibrillation, familial, 11.

What condition is associated with GJA5 p.Val85= (c.255C>A)?

GJA5 p.Val85= (c.255C>A) is associated with atrial fibrillation, familial, 11, atrial standstill 1 (ClinVar).

How common is GJA5 p.Val85= (c.255C>A) in the general population?

GJA5 p.Val85= (c.255C>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is Hereditary atrial fibrillation inherited?

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

GJA5 p.Val85=

c.255C>A · rs782394288 · VCV1967725

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

atrial fibrillation, familial, 11

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 -1.8	GERP -4.8
Overall
CADD	1.354	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,034 alleles

Overall 6.19e-05% 1/1,614,228 alleles · very rare exomes 1/1,461,872 · genomes 0/152,356 · joint denominator

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: GJA5
Protein: p.Val85=
Coding: c.255C>A
MANE Select: NM_181703
dbSNP: rs782394288
Type: single nucleotide variant
Location: chr1:147758984 (GRCh38)
Gene constraint: LOEUF 0.765 · pLI 0.50 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 70.35
Residue 85: a UniProt-annotated variant site (in atfb11)

Full GJA5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

atrial fibrillation, familial, 11 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: atrial standstill 1

For Hereditary atrial fibrillation (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

GJA5 p.Val85Ile Pathogenic ⚠ same residue
GJA5 c.*22G>A Uncertain significance ★★ same condition
GJA5 p.Ala216Thr Uncertain significance ★★ ⚠ same condition
GJA5 p.Ala347Pro Uncertain significance ★★ ⚠ same condition
GJA5 p.Ala96Ser Uncertain significance ★★ ⚠ same condition
GJA5 p.Ala96Val Uncertain significance ★★ ⚠ same condition
GJA5 p.Arg101His Uncertain significance ★★ ⚠ same condition
GJA5 p.Arg106Leu 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/gja5-p-val85 (accessed [today's date]).

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