Is KCNE2 p.Val65= (c.195G>T) pathogenic?

KCNE2 p.Val65= (c.195G>T) is classified Likely benign in KCNE2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-04). Ultra-rare (popmax 0.025%, amr); Associated with Cardiovascular phenotype.

What condition is associated with KCNE2 p.Val65= (c.195G>T)?

KCNE2 p.Val65= (c.195G>T) is associated with Cardiovascular phenotype, long QT syndrome 6 (ClinVar).

How common is KCNE2 p.Val65= (c.195G>T) in the general population?

KCNE2 p.Val65= (c.195G>T) is ultra-rare (popmax 0.025%, amr) (gnomAD).

KCNE2 p.Val65=

c.195G>T · rs765797117 · VCV1783404

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.025%, amr)

Conditions

Cardiovascular phenotype

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 -3.2	GERP -3.9
Overall
CADD	0.594	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.025% Admixed American · 15/59,990 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0124%

Overall 0.00118% 19/1,614,054 alleles · ultra-rare exomes 17/1,461,890 · genomes 2/152,164 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.025%	3,999
European (non-Finnish)	0.000339%	295,010

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: KCNE2
Protein: p.Val65=
Coding: c.195G>T
MANE Select: NM_172201
dbSNP: rs765797117
Type: single nucleotide variant
Location: chr21:34370673 (GRCh38)
Gene constraint: LOEUF 1.636 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 78.41 · 1 PDB
Residue 65: a UniProt-annotated variant site (in lqt6; uncertain significance); a UniProt-annotated variant site (in lqt6); an α-helix

Full KCNE2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: long QT syndrome 6

Similar variants

KCNE2 p.Val65Leu Uncertain significance ★★ ⚠ same residue
KCNE2 c.-13+5G>A Uncertain significance ★★ same condition
KCNE2 c.*234G>A Uncertain significance ★★ same condition
KCNE2 p.Ala66Val Uncertain significance ★★ same condition
KCNE2 p.Asn6Ser Uncertain significance ★★ ⚠ same condition
KCNE2 p.Asn81Lys Uncertain significance ★★ ⚠ same condition
KCNE2 p.Asn81Ser Uncertain significance ★★ ⚠ same condition
KCNE2 p.Gln38Lys 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/kcne2-p-val65 (accessed [today's date]).

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