Is PDYN p.Ser240fs (c.717del) pathogenic?

PDYN p.Ser240fs (c.717del) is classified Uncertain significance in PDYN (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-27). Very rare (popmax 0.005%, amr).

How common is PDYN p.Ser240fs (c.717del) in the general population?

PDYN p.Ser240fs (c.717del) is very rare (popmax 0.005%, amr) (gnomAD).

PDYN p.Ser240fs

c.717del · VCV4883724

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 9	GERP 2.8, phastCons 1
Overall
CADD	28.1	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/59,994 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000248% 4/1,613,992 alleles · very rare exomes 2/1,461,892 · genomes 2/152,100 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,998
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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.Ser240fs
Coding: c.717del
MANE Select: NM_024411
Type: Deletion
Location: chr20:1980371 (GRCh38)

Full PDYN gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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-ser240fs (accessed [today's date]).

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