Is PDYN p.Arg231Trp (c.691C>T) pathogenic?

PDYN p.Arg231Trp (c.691C>T) is classified Uncertain significance in PDYN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-30). AlphaMissense: likely pathogenic (0.8245); Ultra-rare (popmax 0.0164%, mid); Associated with Inborn genetic diseases.

What condition is associated with PDYN p.Arg231Trp (c.691C>T)?

PDYN p.Arg231Trp (c.691C>T) is associated with Inborn genetic diseases, spinocerebellar ataxia type 23 (ClinVar).

How common is PDYN p.Arg231Trp (c.691C>T) in the general population?

PDYN p.Arg231Trp (c.691C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about PDYN p.Arg231Trp (c.691C>T)?

AlphaMissense predicts likely pathogenic (score 0.8245) — an in-silico prediction, not a clinical call.

PDYN p.Arg231Trp

c.691C>T · rs201204862 · VCV898117

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8245 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8245	likely pathogenic
REVEL	0.852	moderately pathogenic-leaning
SaProt	LLR -14.56	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
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
Regional constraint	o/e 1.06	unconstrained · MANE · 2,758 bp · p 0.27 · regional, not allelic
Overall
CADD	25.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.0013% 21/1,614,004 alleles · ultra-rare exomes 18/1,461,876 · genomes 3/152,128 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
South Asian	0.00329%	30,360
African / African-American	0.00267%	37,447
Remaining individualsnot grpmax-eligible	0.0016%	62,488
European (non-Finnish)	0.00119%	84,288

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.Arg231Trp
Coding: c.691C>T
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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: spinocerebellar ataxia type 23

Similar variants

PDYN p.Arg231= Conflicting classifications of pathogenicity ★ same residue
PDYN p.Arg231Gln Uncertain significance ★ ⚠ same residue
PDYN p.Ala190Ser Uncertain significance ★★ ⚠ same condition
PDYN p.Ala20Val Uncertain significance ★★ ⚠ same condition
PDYN p.Arg180Cys Uncertain significance ★★ ⚠ same condition
PDYN p.Arg180Ser Uncertain significance ★★ ⚠ same condition
PDYN p.Cys45Trp Uncertain significance ★★ ⚠ same condition
PDYN p.Glu242Lys 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/pdyn-p-arg231trp (accessed [today's date]).

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