Is PDYN p.Arg231= (c.691C>A) pathogenic?

PDYN p.Arg231= (c.691C>A) is classified Conflicting classifications of pathogenicity in PDYN (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-12-17). Ultra-rare (popmax 0.0136%, nfe); Associated with spinocerebellar ataxia type 23.

What condition is associated with PDYN p.Arg231= (c.691C>A)?

PDYN p.Arg231= (c.691C>A) is associated with spinocerebellar ataxia type 23 (ClinVar).

How common is PDYN p.Arg231= (c.691C>A) in the general population?

PDYN p.Arg231= (c.691C>A) is ultra-rare (popmax 0.0136%, 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.Arg231=

c.691C>A · rs201204862 · VCV586213

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0136%, nfe)

Conditions

spinocerebellar ataxia type 23

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.9	GERP -2.9, phastCons 1
Overall
CADD	7.622	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0136% European (non-Finnish) · 161/1,180,024 alleles

Filtering AF 0.0119% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0112%

Overall 0.0107% 173/1,614,122 alleles · ultra-rare exomes 153/1,461,878 · genomes 20/152,244 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0136%	7,329
Finnishnot grpmax-eligible	0.00937%	10,672
Admixed American	0.005%	20,007
Remaining individualsnot grpmax-eligible	0.0048%	20,837

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.Arg231=
Coding: c.691C>A
MANE Select: NM_024411
dbSNP: rs201204862
Type: single nucleotide variant
Location: chr20:1980397 (GRCh38)
Gene constraint: LOEUF 0.769 · pLI 0.49 (gnomAD)
Structure: AlphaFold pLDDT 58.95 · 8 PDB

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

Similar variants

PDYN p.Arg231Trp Uncertain significance ★★ ⚠ same residue
PDYN p.Arg231Gln Uncertain significance ★ ⚠ same residue
PDYN p.Arg180Cys Uncertain significance ★★ ⚠ same condition
PDYN p.Glu242Lys Uncertain significance ★★ ⚠ same condition
PDYN p.Gly191Trp Uncertain significance ★★ ⚠ same condition
PDYN c.*1030C>T Benign ★★ same condition
PDYN c.*356T>C Benign ★★ same condition
PDYN c.*743T>C Benign ★★ 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/pdyn-p-arg231 (accessed [today's date]).

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