Is PDYN p.Asp243Val (c.728A>T) pathogenic?

PDYN p.Asp243Val (c.728A>T) is classified Uncertain significance in PDYN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-30). AlphaMissense: likely benign (0.2544); Very rare (popmax 0.01%, amr); Associated with Inborn genetic diseases.

What condition is associated with PDYN p.Asp243Val (c.728A>T)?

PDYN p.Asp243Val (c.728A>T) is associated with Inborn genetic diseases (ClinVar).

How common is PDYN p.Asp243Val (c.728A>T) in the general population?

PDYN p.Asp243Val (c.728A>T) is very rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about PDYN p.Asp243Val (c.728A>T)?

AlphaMissense predicts likely benign (score 0.2544) — an in-silico prediction, not a clinical call.

PDYN p.Asp243Val

c.728A>T · VCV3416715

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2544 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.01%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2544	likely benign
REVEL	0.591	indeterminate
SaProt	LLR -7.33	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.1	GERP 0.62, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 2,758 bp · p 0.27 · regional, not allelic
Overall
CADD	21.8	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 0.01% Admixed American · 6/60,018 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.000434% 7/1,614,076 alleles · very rare exomes 5/1,461,892 · genomes 2/152,184 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	10,003
Remaining individualsnot grpmax-eligible	0.0016%	62,506

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.Asp243Val
Coding: c.728A>T
MANE Select: NM_024411
Type: single nucleotide variant
Location: chr20:1980360 (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.Asp243Asn Uncertain significance ★ ⚠ same residue
PDYN p.Asp243= Likely benign ★ 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

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-asp243val (accessed [today's date]).

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