Is PNKD p.Ala26Val (c.77C>T) pathogenic?

PNKD p.Ala26Val (c.77C>T) is classified Uncertain significance in PNKD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-18). AlphaMissense: likely benign (0.1879); Very rare (popmax 8.48e-05%, nfe); Associated with paroxysmal nonkinesigenic dyskinesia.

What condition is associated with PNKD p.Ala26Val (c.77C>T)?

PNKD p.Ala26Val (c.77C>T) is associated with paroxysmal nonkinesigenic dyskinesia (ClinVar).

How common is PNKD p.Ala26Val (c.77C>T) in the general population?

PNKD p.Ala26Val (c.77C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

How is Paroxysmal non-kinesigenic dyskinesia inherited?

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

What do computational predictors say about PNKD p.Ala26Val (c.77C>T)?

AlphaMissense predicts likely benign (score 0.1879) — an in-silico prediction, not a clinical call.

PNKD p.Ala26Val

c.77C>T · rs767501883 · VCV2004908

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1879 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

paroxysmal nonkinesigenic dyskinesia

Computational evidence

Protein change
AlphaMissense	0.1879	likely benign
REVEL	0.249	benign-leaning
SaProt	LLR -6.93	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP 2.3, phastCons 0.21
Regional constraint	o/e 1.01	unconstrained · MANE · 74 kb · p 0.84 · regional, not allelic
Overall
CADD	22.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,650 alleles

Overall 6.2e-05% 1/1,613,752 alleles · very rare exomes 1/1,461,436 · genomes 0/152,316 · 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: PNKD
Protein: p.Ala26Val
Coding: c.77C>T
MANE Select: NM_015488
dbSNP: rs767501883
Type: single nucleotide variant
Location: chr2:218271390 (GRCh38)
Gene constraint: LOEUF 1.131 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.69

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

Disease context

paroxysmal nonkinesigenic dyskinesia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Paroxysmal non-kinesigenic dyskinesia (Orphanet):

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

Similar variants

PNKD p.Ala26Thr Uncertain significance ★ ⚠ same residue
PNKD p.Ala26fs Conflicting classifications of pathogenicity ★ same residue
PNKD c.465+3G>A Uncertain significance ★★ same condition
PNKD p.Ala167Thr Uncertain significance ★★ ⚠ same condition
PNKD p.Ala28Gly Uncertain significance ★★ ⚠ same condition
PNKD p.Ala78Val Uncertain significance ★★ ⚠ same condition
PNKD p.Arg368Gln Uncertain significance ★★ ⚠ same condition
PNKD p.Asp365Val 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/pnkd-p-ala26val (accessed [today's date]).

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