Is DSP p.Ser299= (c.897C>T) pathogenic?

DSP p.Ser299= (c.897C>T) is classified Benign/Likely benign in DSP (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-02-12). Very rare (popmax 0.00439%, sas); Associated with Cardiovascular phenotype.

What condition is associated with DSP p.Ser299= (c.897C>T)?

DSP p.Ser299= (c.897C>T) is associated with Cardiovascular phenotype, cardiomyopathy, arrhythmogenic cardiomyopathy with wooly hair and keratoderma (ClinVar).

How common is DSP p.Ser299= (c.897C>T) in the general population?

DSP p.Ser299= (c.897C>T) is very rare (popmax 0.00439%, sas) (gnomAD).

DSP p.Ser299=

c.897C>T · rs121912992 · VCV188456

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8.5	GERP -4.3
Overall
CADD	9.32	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00439% South Asian · 4/91,074 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.00601% 97/1,613,980 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.119%	842
Remaining individualsnot grpmax-eligible	0.0048%	20,835
South Asiangrpmax	0.00439%	22,769
Admixed American	0.00333%	30,000
African / African-American	0.00267%	37,497
East Asian	0.00223%	44,882
European (non-Finnish)	0.000763%	131,106

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser299=
Coding: c.897C>T
MANE Select: NM_004415
dbSNP: rs121912992
Type: single nucleotide variant
Location: chr6:7565478 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 299: the 'globular 1' region; the 'interaction with mapre1' region; the 'interaction with jup and pkp2' region; the 'interaction with pkp1' region; a UniProt-annotated variant site (in arvd8; uncertain significance); a UniProt-annotated variant site (in dcwhkta; uncertain significance); a UniProt-annotated variant site (in arvd8; likely pathogenic; results in an unstable protein that forms perinuclear aggregates); a UniProt-annotated variant site (in arvd8 and dcwhkta; uncertain significance)

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

Similar variants

DSP p.Ser299Arg Pathogenic same residue
DSP p.Ser299Gly Uncertain significance ★ same residue
DSP c.1141-2A>T Likely pathogenic ★★ same condition
DSP c.1266+2T>C Likely pathogenic ★★ same condition
DSP c.1574+1G>A Likely pathogenic ★★ same condition
DSP c.2130+1G>A Pathogenic/Likely pathogenic ★★ same condition
DSP c.2297+1G>A Likely pathogenic ★★ same condition
DSP c.2298-1G>C Likely pathogenic ★★ 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/dsp-p-ser299 (accessed [today's date]).

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