Is GJA5 p.Phe10= (c.30C>T) pathogenic?

GJA5 p.Phe10= (c.30C>T) is classified Likely benign in GJA5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-05). Very rare (popmax 0.00329%, sas); Associated with atrial standstill 1.

What condition is associated with GJA5 p.Phe10= (c.30C>T)?

GJA5 p.Phe10= (c.30C>T) is associated with atrial standstill 1, atrial fibrillation, familial, 11 (ClinVar).

How common is GJA5 p.Phe10= (c.30C>T) in the general population?

GJA5 p.Phe10= (c.30C>T) is very rare (popmax 0.00329%, sas) (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.Phe10=

c.30C>T · rs1350829557 · VCV2059443

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

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 -1.8, phastCons 1
Overall
CADD	4.417	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,086 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.00031% 5/1,613,860 alleles · very rare exomes 4/1,461,698 · genomes 1/152,162 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,362
African / African-American	0.00134%	74,906
European (non-Finnish)	8.48e-05%	1,179,924

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.Phe10=
Coding: c.30C>T
MANE Select: NM_181703
dbSNP: rs1350829557
Type: single nucleotide variant
Location: chr1:147759209 (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.Phe10Leu 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-phe10 (accessed [today's date]).

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