Is PDYN p.Pro91Ser (c.271C>T) pathogenic?

PDYN p.Pro91Ser (c.271C>T) is classified Conflicting classifications of pathogenicity in PDYN (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-07-21). AlphaMissense: likely benign (0.0746); Ultra-rare (popmax 0.0908%, afr); Associated with Inborn genetic diseases.

What condition is associated with PDYN p.Pro91Ser (c.271C>T)?

PDYN p.Pro91Ser (c.271C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PDYN p.Pro91Ser (c.271C>T) in the general population?

PDYN p.Pro91Ser (c.271C>T) is ultra-rare (popmax 0.0908%, afr) (gnomAD).

What do computational predictors say about PDYN p.Pro91Ser (c.271C>T)?

AlphaMissense predicts likely benign (score 0.0746) — an in-silico prediction, not a clinical call.

PDYN p.Pro91Ser

c.271C>T · rs147355936 · VCV2428318

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0746 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0908%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0746	likely benign
REVEL	0.069	moderately benign-leaning
SaProt	LLR -5.05	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 -3.5, phastCons 0.064
Regional constraint	o/e 1.06	unconstrained · MANE · 2,758 bp · p 0.27 · regional, not allelic
Overall
CADD	7.875	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0908% African / African-American · 68/74,910 alleles

Filtering AF 0.0734% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0671%

Overall 0.0044% 71/1,614,072 alleles · ultra-rare exomes 29/1,461,890 · genomes 42/152,182 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0908%	1,102
Remaining individualsnot grpmax-eligible	0.0048%	20,830

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.Pro91Ser
Coding: c.271C>T
MANE Select: NM_024411
dbSNP: rs147355936
Type: single nucleotide variant
Location: chr20:1980817 (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.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
PDYN p.Gly199Ala 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-pro91ser (accessed [today's date]).

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