Is KCNC3 p.Gly643= (c.1929C>T) pathogenic?

KCNC3 p.Gly643= (c.1929C>T) is classified Benign/Likely benign in KCNC3 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-02). Low-frequency (popmax 2.33%, afr); Associated with spinocerebellar ataxia type 13.

What condition is associated with KCNC3 p.Gly643= (c.1929C>T)?

KCNC3 p.Gly643= (c.1929C>T) is associated with spinocerebellar ataxia type 13 (ClinVar).

How common is KCNC3 p.Gly643= (c.1929C>T) in the general population?

KCNC3 p.Gly643= (c.1929C>T) is low-frequency (popmax 2.33%, afr) (gnomAD).

How is Spinocerebellar ataxia type 13 inherited?

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

KCNC3 p.Gly643=

c.1929C>T · rs111744086 · VCV288184

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.33%, afr)

Conditions

spinocerebellar ataxia type 13

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	GERP -2.3
Overall
CADD	1.595	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.33% African / African-American · 1,704/73,084 alleles

Filtering AF 2.24% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.2%

Overall 1.08% 16,748/1,545,834 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.33%	43
Admixed American	1.29%	77
European (non-Finnish)	1.11%	90
Remaining individualsnot grpmax-eligible	1.11%	90
Middle Eastern	1.02%	98
Ashkenazi Jewishnot grpmax-eligible	0.803%	125
Finnishnot grpmax-eligible	0.763%	131
South Asian	0.319%	314
East Asian	0.00489%	20,451

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: KCNC3
Protein: p.Gly643=
Coding: c.1929C>T
MANE Select: NM_004977
dbSNP: rs111744086
Type: single nucleotide variant
Location: chr19:50323024 (GRCh38)
Gene constraint: LOEUF 0.654 · pLI 0.30 (gnomAD)
Structure: AlphaFold pLDDT 66.01
Residue 643: a UniProt-annotated variant site (in sca13; uncertain significance; no effect on channel activity)

Full KCNC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

spinocerebellar ataxia type 13 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Spinocerebellar ataxia type 13 (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

KCNC3 p.Gly643Ser Benign/Likely benign ★★ same residue
KCNC3 p.Arg420His Pathogenic ★★ same condition
KCNC3 p.Arg423His Pathogenic ★★ same condition
KCNC3 p.Ala749Thr Uncertain significance ★★ ⚠ same condition
KCNC3 p.Gly231Ser Uncertain significance ★★ ⚠ same condition
KCNC3 p.Gly251Ser Uncertain significance ★★ ⚠ same condition
KCNC3 p.Gly331Arg Uncertain significance ★★ ⚠ same condition
KCNC3 p.Gly47Asp 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/kcnc3-p-gly643 (accessed [today's date]).

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