Is GJA5 p.Pro189= (c.567C>G) pathogenic?

GJA5 p.Pro189= (c.567C>G) is classified Likely benign in GJA5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-27). Very rare (popmax 0.000508%, nfe); Associated with atrial standstill 1.

What condition is associated with GJA5 p.Pro189= (c.567C>G)?

GJA5 p.Pro189= (c.567C>G) is associated with atrial standstill 1, atrial fibrillation, familial, 11 (ClinVar).

How common is GJA5 p.Pro189= (c.567C>G) in the general population?

GJA5 p.Pro189= (c.567C>G) is very rare (popmax 0.000508%, nfe) (gnomAD).

How is Isolated atrial standstill inherited?

Typically Autosomal dominant, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

GJA5 p.Pro189=

c.567C>G · rs2148959089 · VCV1532181

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000508%, nfe)

Conditions

atrial standstill 1

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 2.6	GERP 0.46, phastCons 1
Overall
CADD	8.963	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000508% European (non-Finnish) · 6/1,180,030 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,614,216 alleles · very rare exomes 6/1,461,866 · genomes 0/152,350 · 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.Pro189=
Coding: c.567C>G
MANE Select: NM_181703
dbSNP: rs2148959089
Type: single nucleotide variant
Location: chr1:147758672 (GRCh38)
Gene constraint: LOEUF 0.765 · pLI 0.50 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 70.35

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

Disease context

atrial standstill 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: atrial fibrillation, familial, 11

For Isolated atrial standstill (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: Adult

Similar variants

GJA5 p.Pro189Arg Uncertain significance ★ ⚠ 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-pro189 (accessed [today's date]).

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