Is PDYN p.Ser27Phe (c.80C>T) pathogenic?

PDYN p.Ser27Phe (c.80C>T) is classified Uncertain significance in PDYN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-04-20). AlphaMissense: likely benign (0.2665); Very rare (popmax 0.00136%, nfe).

How common is PDYN p.Ser27Phe (c.80C>T) in the general population?

PDYN p.Ser27Phe (c.80C>T) is very rare (popmax 0.00136%, nfe) (gnomAD).

What do computational predictors say about PDYN p.Ser27Phe (c.80C>T)?

AlphaMissense predicts likely benign (score 0.2665) — an in-silico prediction, not a clinical call.

PDYN p.Ser27Phe

c.80C>T · rs536626217 · VCV1693759

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2665 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00136%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2665	likely benign
REVEL	0.568	indeterminate
SaProt	LLR -7.66	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 7.5	GERP 1.3, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 2,758 bp · p 0.27 · regional, not allelic
Overall
CADD	20.6	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 0.00136% European (non-Finnish) · 16/1,179,996 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.000991% 16/1,613,956 alleles · very rare exomes 15/1,461,784 · genomes 1/152,172 · 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.Ser27Phe
Coding: c.80C>T
MANE Select: NM_024411
dbSNP: rs536626217
Type: single nucleotide variant
Location: chr20:1983005 (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.Ser27Cys Uncertain significance ★ same residue
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

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-ser27phe (accessed [today's date]).

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