Is KCND3 p.Pro161= (c.483C>T) pathogenic?

KCND3 p.Pro161= (c.483C>T) is classified Likely benign in KCND3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-05-08). Very rare (popmax 0.00102%, nfe); Associated with spinocerebellar ataxia type 19/22.

What condition is associated with KCND3 p.Pro161= (c.483C>T)?

KCND3 p.Pro161= (c.483C>T) is associated with spinocerebellar ataxia type 19/22 (ClinVar).

How common is KCND3 p.Pro161= (c.483C>T) in the general population?

KCND3 p.Pro161= (c.483C>T) is very rare (popmax 0.00102%, nfe) (gnomAD).

How is Spinocerebellar ataxia type 19/22 inherited?

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

KCND3 p.Pro161=

c.483C>T · VCV4683365

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00102%, nfe)

Conditions

spinocerebellar ataxia type 19/22

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 -1.6	GERP -4.2
Overall
CADD	5.846	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00102% European (non-Finnish) · 12/1,180,038 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000743% 12/1,614,014 alleles · very rare exomes 8/1,461,886 · genomes 4/152,128 · 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: KCND3
Protein: p.Pro161=
Coding: c.483C>T
MANE Select: NM_001378969
Type: single nucleotide variant
Location: chr1:111982244 (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

spinocerebellar ataxia type 19/22 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Spinocerebellar ataxia type 19/22 (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

KCND3 p.Pro161Ser Uncertain significance ★ ⚠ same residue
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.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-pro161 (accessed [today's date]).

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