Is PDYN p.Ala52Asp (c.155C>A) pathogenic?

PDYN p.Ala52Asp (c.155C>A) is classified Uncertain significance in PDYN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-14). AlphaMissense: likely benign (0.1284); Very rare (popmax 6.2e-05%); Associated with Inborn genetic diseases.

What condition is associated with PDYN p.Ala52Asp (c.155C>A)?

PDYN p.Ala52Asp (c.155C>A) is associated with Inborn genetic diseases (ClinVar).

How common is PDYN p.Ala52Asp (c.155C>A) in the general population?

PDYN p.Ala52Asp (c.155C>A) is very rare (popmax 6.2e-05%) (gnomAD).

What do computational predictors say about PDYN p.Ala52Asp (c.155C>A)?

AlphaMissense predicts likely benign (score 0.1284) — an in-silico prediction, not a clinical call.

PDYN p.Ala52Asp

c.155C>A · VCV3930510

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1284 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1284	likely benign
REVEL	0.266	benign-leaning
SaProt	LLR -5.69	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 -0.77, phastCons 0.001
Regional constraint	o/e 1.06	unconstrained · MANE · 2,758 bp · p 0.27 · regional, not allelic
Overall
CADD	13.95	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 6.2e-05%

Overall 6.2e-05% 1/1,614,014 alleles · very rare exomes 0/1,461,810 · genomes 1/152,204 · 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.Ala52Asp
Coding: c.155C>A
MANE Select: NM_024411
Type: single nucleotide variant
Location: chr20:1980933 (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

Similar variants

PDYN p.Ala52Thr Uncertain significance ★ ⚠ same residue
PDYN p.Ala190Ser Uncertain significance ★★ ⚠ same condition
PDYN p.Ala20Val Uncertain significance ★★ ⚠ same condition
PDYN p.Arg180Ser Uncertain significance ★★ ⚠ same condition
PDYN p.Arg231Trp Uncertain significance ★★ ⚠ same condition
PDYN p.Cys45Trp Uncertain significance ★★ ⚠ same condition
PDYN p.Glu242Lys Uncertain significance ★★ ⚠ same condition
PDYN p.Gly191Trp 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-ala52asp (accessed [today's date]).

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