Is DSP p.Arg2838Pro (c.8513G>C) pathogenic?

DSP p.Arg2838Pro (c.8513G>C) is classified Uncertain significance in DSP (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-17). AlphaMissense: ambiguous (0.5219); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with DSP p.Arg2838Pro (c.8513G>C)?

DSP p.Arg2838Pro (c.8513G>C) is associated with Cardiovascular phenotype (ClinVar).

How common is DSP p.Arg2838Pro (c.8513G>C) in the general population?

DSP p.Arg2838Pro (c.8513G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DSP p.Arg2838Pro (c.8513G>C)?

AlphaMissense predicts ambiguous (score 0.5219) — an in-silico prediction, not a clinical call.

DSP p.Arg2838Pro

c.8513G>C · VCV4840032

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5219 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.5219	ambiguous
REVEL	0.402	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 1,308 bp · p 0.26 · regional, not allelic
Overall
CADD	24.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DSP
Protein: p.Arg2838Pro
Coding: c.8513G>C
MANE Select: NM_004415
Type: single nucleotide variant
Location: chr6:7585775 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2838: 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 'disordered' region; the '6 x 4 aa tandem repeats of g-s-r-[sr]' region; a modified residue (asymmetric dimethylarginine; by prmt1); 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.Arg2838His Uncertain significance ★★ same residue
DSP p.Arg2838Cys Conflicting classifications of pathogenicity ★ 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

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-arg2838pro (accessed [today's date]).

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