Is DSP p.Ser2807= (c.8421C>T) pathogenic?

DSP p.Ser2807= (c.8421C>T) is classified Likely benign in DSP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-04). Ultra-rare (popmax 0.033%, mid); Associated with Cardiovascular phenotype.

What condition is associated with DSP p.Ser2807= (c.8421C>T)?

DSP p.Ser2807= (c.8421C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is DSP p.Ser2807= (c.8421C>T) in the general population?

DSP p.Ser2807= (c.8421C>T) is ultra-rare (popmax 0.033%, mid) (gnomAD).

DSP p.Ser2807=

c.8421C>T · rs752007344 · VCV3224255

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

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 -14	GERP -3.8
Overall
CADD	0.081	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.033% Middle Eastern · 2/6,060 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.000372% 6/1,614,198 alleles · ultra-rare exomes 6/1,461,882 · genomes 0/152,316 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,030
South Asian	0.0011%	91,084
European (non-Finnish)	0.000254%	393,345

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.Ser2807=
Coding: c.8421C>T
MANE Select: NM_004415
dbSNP: rs752007344
Type: single nucleotide variant
Location: chr6:7585683 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2807: a UniProt-annotated variant site (in arvd8; uncertain significance); a UniProt-annotated variant site (in dcwhkta; uncertain significance); a UniProt-annotated variant site (in dcwhk; uncertain significance; abolishes expression in the myocardium); a UniProt-annotated variant site (in ebla; uncertain significance); a UniProt-annotated variant site (in dcwhk; uncertain significance); the 'binds to telomeres' region; the 'globular 2' region; the '4.5 x 38 aa tandem repeats (domain c)' region; 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); a UniProt-annotated variant site (in arvd8)

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

Similar variants

DSP p.Ser2807Pro Uncertain significance ★ same residue
DSP c.778-2A>G Likely pathogenic ★★ same condition
DSP p.Arg1267Ter Pathogenic/Likely pathogenic ★★ same condition
DSP p.Arg160Ter Pathogenic/Likely pathogenic ★★ same condition
DSP p.Arg1738Ter Pathogenic ★★ same condition
DSP p.Arg270Ter Pathogenic/Likely pathogenic ★★ same condition
DSP p.Arg425Ter Pathogenic/Likely pathogenic ★★ same condition
DSP p.Arg941Ter Pathogenic/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-ser2807 (accessed [today's date]).

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