Is KCND3 p.Pro211= (c.633G>T) pathogenic?

KCND3 p.Pro211= (c.633G>T) is classified Benign/Likely benign in KCND3 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-23). Rare (popmax 0.197%, afr); Associated with Cardiovascular phenotype.

What condition is associated with KCND3 p.Pro211= (c.633G>T)?

KCND3 p.Pro211= (c.633G>T) is associated with Cardiovascular phenotype, spinocerebellar ataxia type 19/22 (ClinVar).

How common is KCND3 p.Pro211= (c.633G>T) in the general population?

KCND3 p.Pro211= (c.633G>T) is rare (popmax 0.197%, afr) (gnomAD).

KCND3 p.Pro211=

c.633G>T · rs35131566 · VCV240083

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.197%, afr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -6.4	GERP -4.2
Overall
CADD	0.501	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.197% African / African-American · 148/74,958 alleles

Filtering AF 0.171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.162%

Overall 0.0114% 184/1,613,608 alleles · rare exomes 81/1,461,658 · genomes 103/151,950 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.197%	506
Admixed American	0.0283%	3,529
Remaining individualsnot grpmax-eligible	0.0176%	5,682
Middle Eastern	0.0165%	6,062
South Asian	0.0022%	45,521
European (non-Finnish)	0.000424%	235,987

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: KCND3
Protein: p.Pro211=
Coding: c.633G>T
MANE Select: NM_001378969
dbSNP: rs35131566
Type: single nucleotide variant
Location: chr1:111982094 (GRCh38)
Gene constraint: LOEUF 0.303 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.32 · 6 PDB

Full KCND3 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: spinocerebellar ataxia type 19/22

Similar variants

KCND3 p.Arg290Gln Likely pathogenic ★★ same condition
KCND3 p.Gly384Ser Pathogenic/Likely pathogenic ★★ same condition
KCND3 p.Pro375Ser Pathogenic/Likely pathogenic ★★ same condition
KCND3 p.Thr377Met Pathogenic ★★ same condition
KCND3 p.Val392Ile Pathogenic/Likely pathogenic ★★ same condition
KCND3 p.Ala144Thr Uncertain significance ★★ ⚠ same condition
KCND3 p.Ala15Val Uncertain significance ★★ ⚠ same condition
KCND3 p.Ala172Thr 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/kcnd3-p-pro211 (accessed [today's date]).

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