Is PDYN p.Asp135= (c.405C>T) pathogenic?

PDYN p.Asp135= (c.405C>T) is classified Likely benign in PDYN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-03). Ultra-rare (popmax 0.0142%, nfe); Associated with spinocerebellar ataxia type 23.

What condition is associated with PDYN p.Asp135= (c.405C>T)?

PDYN p.Asp135= (c.405C>T) is associated with spinocerebellar ataxia type 23 (ClinVar).

How common is PDYN p.Asp135= (c.405C>T) in the general population?

PDYN p.Asp135= (c.405C>T) is ultra-rare (popmax 0.0142%, nfe) (gnomAD).

How is Spinocerebellar ataxia type 23 inherited?

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

PDYN p.Asp135=

c.405C>T · rs147181436 · VCV337840

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0142%, nfe)

Conditions

spinocerebellar ataxia type 23

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -1.1	GERP -4.5
Overall
CADD	0.514	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0142% European (non-Finnish) · 168/1,180,036 alleles

Filtering AF 0.0125% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0118%

Overall 0.0127% 205/1,614,154 alleles · ultra-rare exomes 182/1,461,888 · genomes 23/152,266 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0142%	7,024
Finnishnot grpmax-eligible	0.0141%	7,115
Remaining individualsnot grpmax-eligible	0.0128%	7,814
Admixed American	0.0117%	8,573
East Asian	0.00669%	14,956
African / African-American	0.00666%	15,005
South Asian	0.00549%	18,216

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: PDYN
Protein: p.Asp135=
Coding: c.405C>T
MANE Select: NM_024411
dbSNP: rs147181436
Type: single nucleotide variant
Location: chr20:1980683 (GRCh38)

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

Disease context

spinocerebellar ataxia type 23 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Spinocerebellar ataxia type 23 (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

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/pdyn-p-asp135 (accessed [today's date]).

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