Is KCNA5 p.Pro73= (c.219G>A) pathogenic?

KCNA5 p.Pro73= (c.219G>A) is classified Likely benign in KCNA5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-01). Very rare (popmax 0.00135%, afr); Associated with atrial fibrillation, familial, 7.

What condition is associated with KCNA5 p.Pro73= (c.219G>A)?

KCNA5 p.Pro73= (c.219G>A) is associated with atrial fibrillation, familial, 7 (ClinVar).

How common is KCNA5 p.Pro73= (c.219G>A) in the general population?

KCNA5 p.Pro73= (c.219G>A) is very rare (popmax 0.00135%, afr) (gnomAD).

How is Hereditary atrial fibrillation inherited?

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

KCNA5 p.Pro73=

c.219G>A · rs200192209 · VCV2105127

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00135%, afr)

Conditions

atrial fibrillation, familial, 7

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 -1.5	GERP -1.6
Overall
CADD	7.567	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00135% African / African-American · 1/73,896 alleles

Overall 0.000129% 2/1,556,062 alleles · very rare exomes 1/1,403,720 · genomes 1/152,342 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00135%	73,896
European (non-Finnish)	8.65e-05%	1,156,620

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: KCNA5
Protein: p.Pro73=
Coding: c.219G>A
MANE Select: NM_002234
dbSNP: rs200192209
Type: single nucleotide variant
Location: chr12:5044366 (GRCh38)
Gene constraint: LOEUF 1.182 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.64
Residue 73: the 'tetramerization domain' region; the 'disordered' region; the '2 x 11 aa tandem repeat of d-[sp]-g-v-r-p-l-p-p-l-p' region

Full KCNA5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

atrial fibrillation, familial, 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary atrial fibrillation (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

KCNA5 p.Pro73Ser Uncertain significance ★ ⚠ same residue
KCNA5 c.-52G>T Uncertain significance ★★ same condition
KCNA5 c.*244C>T Uncertain significance ★★ same condition
KCNA5 c.*782G>A Uncertain significance ★★ same condition
KCNA5 p.Ala293Thr Uncertain significance ★★ ⚠ same condition
KCNA5 p.Ala295Ser Uncertain significance ★★ ⚠ same condition
KCNA5 p.Ala305Thr Uncertain significance ★★ ⚠ same condition
KCNA5 p.Ala397Thr 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/kcna5-p-pro73 (accessed [today's date]).

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