Is PDYN p.Ala9Ser (c.25G>T) pathogenic?

PDYN p.Ala9Ser (c.25G>T) is classified Uncertain significance in PDYN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-19). AlphaMissense: likely benign (0.1519); Very rare (popmax 0.00167%, amr).

How common is PDYN p.Ala9Ser (c.25G>T) in the general population?

PDYN p.Ala9Ser (c.25G>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about PDYN p.Ala9Ser (c.25G>T)?

AlphaMissense predicts likely benign (score 0.1519) — an in-silico prediction, not a clinical call.

PDYN p.Ala9Ser

c.25G>T · VCV4944102

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1519 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1519	likely benign
REVEL	0.244	benign-leaning
SaProt	LLR -7.70	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.4	GERP -1, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 2,758 bp · p 0.27 · regional, not allelic
Overall
CADD	18.06	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 0.00167% Admixed American · 1/60,022 alleles

Overall 6.2e-05% 1/1,613,292 alleles · very rare exomes 1/1,461,066 · genomes 0/152,226 · 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: PDYN
Protein: p.Ala9Ser
Coding: c.25G>T
MANE Select: NM_024411
Type: single nucleotide variant
Location: chr20:1983060 (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

Similar variants

PDYN p.Ala190Ser Uncertain significance ★★ ⚠ same type
PDYN p.Ala20Val Uncertain significance ★★ ⚠ same type
PDYN p.Arg180Cys Uncertain significance ★★ ⚠ same type
PDYN p.Arg180Ser Uncertain significance ★★ ⚠ same type
PDYN p.Arg231Trp Uncertain significance ★★ ⚠ same type
PDYN p.Cys45Trp Uncertain significance ★★ ⚠ same type
PDYN p.Glu107Asp Uncertain significance ★★ ⚠ same type
PDYN p.Glu242Lys Uncertain significance ★★ ⚠ same type

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-ala9ser (accessed [today's date]).

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