Is KCTD17 p.Pro259= (c.777C>T) pathogenic?

KCTD17 p.Pro259= (c.777C>T) is classified Likely benign in KCTD17 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-23). Ultra-rare (popmax 0.0219%, afr); Associated with myoclonic dystonia 26.

What condition is associated with KCTD17 p.Pro259= (c.777C>T)?

KCTD17 p.Pro259= (c.777C>T) is associated with myoclonic dystonia 26 (ClinVar).

How common is KCTD17 p.Pro259= (c.777C>T) in the general population?

KCTD17 p.Pro259= (c.777C>T) is ultra-rare (popmax 0.0219%, afr) (gnomAD).

How is Myoclonus-dystonia syndrome inherited?

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

KCTD17 p.Pro259=

c.777C>T · rs548803912 · VCV1081498

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0219%, afr)

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 -0.41	GERP -2.2, phastCons 0.095
Overall
CADD	10.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0219% African / African-American · 16/73,152 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0111%

Overall 0.00941% 146/1,550,934 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0219%	4,572
European (non-Finnish)	0.0101%	9,886
South Asian	0.00833%	12,007
Remaining individualsnot grpmax-eligible	0.00665%	15,038
Admixed American	0.00392%	25,498
Finnishnot grpmax-eligible	0.00168%	59,406

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.Pro259=
Coding: c.777C>T
MANE Select: NM_001282684
dbSNP: rs548803912
Type: single nucleotide variant
Location: chr22:37061168 (GRCh38)
Gene constraint: LOEUF 0.928 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.59 · 1 PDB
Residue 259: the 'disordered' region

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-pro259 (accessed [today's date]).

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