Is KCTD17 p.Pro299= (c.897C>T) pathogenic?

KCTD17 p.Pro299= (c.897C>T) is classified Benign in KCTD17 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). Common (popmax 6.73%, mid) — too common for a highly-penetrant pathogenic allele; Associated with myoclonic dystonia 26.

What condition is associated with KCTD17 p.Pro299= (c.897C>T)?

KCTD17 p.Pro299= (c.897C>T) is associated with myoclonic dystonia 26 (ClinVar).

How is Myoclonus-dystonia syndrome inherited?

Typically Autosomal dominant, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

KCTD17 p.Pro299=

Q: How common is KCTD17 p.Pro299= (c.897C>T) in the general population?

KCTD17 p.Pro299= (c.897C>T) is common (popmax 6.73%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.897C>T · rs116956945 · VCV476040

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 6.73%, mid) — too common for a highly-penetrant pathogenic allele

Conditions

myoclonic dystonia 26

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 -1.2, phastCons 1
Overall
CADD	13.06	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.73% Middle Eastern · 397/5,896 alleles

Filtering AF 6.19% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.97%

Overall 4.84% 78,101/1,612,974 alleles · common exomes 72,573/1,460,920 · genomes 5,528/152,054 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	9.01%	11
Middle Easterngrpmax	6.73%	15
European (non-Finnish)	5.64%	18
South Asian	4.47%	22
Remaining individualsnot grpmax-eligible	4.32%	23
Admixed American	2.74%	37
Ashkenazi Jewishnot grpmax-eligible	2.51%	40
Finnishnot grpmax-eligible	1.91%	52
African / African-American	0.905%	111
East Asian	0.0178%	5,606

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: KCTD17
Protein: p.Pro299=
Coding: c.897C>T
MANE Select: NM_001282684
dbSNP: rs116956945
Type: single nucleotide variant
Location: chr22:37062546 (GRCh38)
Gene constraint: LOEUF 0.928 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.59 · 1 PDB

Full KCTD17 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

myoclonic dystonia 26 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Myoclonus-dystonia syndrome (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: Adolescent, Adult, Childhood
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

KCTD17 p.Arg138His Pathogenic ★★ same condition
KCTD17 c.486+5G>A Uncertain significance ★★ same condition
KCTD17 p.Ala12Val Uncertain significance ★★ ⚠ same condition
KCTD17 p.Ala298Thr Uncertain significance ★★ ⚠ same condition
KCTD17 p.Arg159Cys Uncertain significance ★★ same condition
KCTD17 p.Arg264Cys Uncertain significance ★★ ⚠ same condition
KCTD17 p.Arg281Pro Uncertain significance ★★ ⚠ same condition
KCTD17 p.Glu146Lys 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/kctd17-p-pro299 (accessed [today's date]).

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