Is DSP p.Ser53Pro (c.157T>C) pathogenic?

DSP p.Ser53Pro (c.157T>C) is classified Conflicting classifications of pathogenicity in DSP (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-10-09). AlphaMissense: likely benign (0.1342); Very rare (popmax 0.00511%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with DSP p.Ser53Pro (c.157T>C)?

DSP p.Ser53Pro (c.157T>C) is associated with Cardiovascular phenotype, cardiomyopathy, arrhythmogenic cardiomyopathy with wooly hair and keratoderma (ClinVar).

How common is DSP p.Ser53Pro (c.157T>C) in the general population?

DSP p.Ser53Pro (c.157T>C) is very rare (popmax 0.00511%, nfe) (gnomAD).

What do computational predictors say about DSP p.Ser53Pro (c.157T>C)?

AlphaMissense predicts likely benign (score 0.1342) — an in-silico prediction, not a clinical call.

DSP p.Ser53Pro

c.157T>C · rs397516918 · VCV1171385

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1342 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00511%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

⚠ 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
AlphaMissense	0.1342	likely benign
REVEL	0.137	moderately benign-leaning
SaProt	LLR -7.09	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5.6	GERP 0.93, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 29 kb · p 0.14 · regional, not allelic
Overall
CADD	20.5	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 0.00511% European (non-Finnish) · 59/1,154,492 alleles

Filtering AF 0.00402% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00368%

Overall 0.0039% 61/1,563,864 alleles · very rare exomes 58/1,411,744 · genomes 3/152,120 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00511%	19,568
Remaining individualsnot grpmax-eligible	0.00165%	60,614
African / African-American	0.00136%	73,590

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: DSP
Protein: p.Ser53Pro
Coding: c.157T>C
MANE Select: NM_004415
dbSNP: rs397516918
Type: single nucleotide variant
Location: chr6:7542072 (GRCh38)

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiomyopathy arrhythmogenic cardiomyopathy with wooly hair and keratoderma arrhythmogenic right ventricular dysplasia 8

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/dsp-p-ser53pro (accessed [today's date]).

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