Is DSP p.Arg141Ser (c.423G>T) pathogenic?

DSP p.Arg141Ser (c.423G>T) is classified Uncertain significance in DSP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-04). AlphaMissense: likely pathogenic (0.8884); Absent from gnomAD v4.1; Associated with cardiomyopathy.

How common is DSP p.Arg141Ser (c.423G>T) in the general population?

DSP p.Arg141Ser (c.423G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DSP p.Arg141Ser (c.423G>T)?

AlphaMissense predicts likely pathogenic (score 0.8884) — an in-silico prediction, not a clinical call.

DSP p.Arg141Ser

Q: What condition is associated with DSP p.Arg141Ser (c.423G>T)?

DSP p.Arg141Ser (c.423G>T) is associated with cardiomyopathy, arrhythmogenic cardiomyopathy with wooly hair and keratoderma, arrhythmogenic right ventricular dysplasia 8 (ClinVar).

c.423G>T · rs771688614 · VCV2140587

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8884 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

cardiomyopathy

Computational evidence

Protein change
AlphaMissense	0.8884	likely pathogenic
REVEL	0.433	indeterminate
Splicing
SpliceAI	Δ0.49	acceptor loss at this position · masked 0 · deltas
Pangolin	Δ0.32	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -0.1	GERP -4.1, phastCons 0.005
Regional constraint	o/e 0.94	unconstrained · MANE · 29 kb · p 0.14 · regional, not allelic
Overall
CADD	8.666	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.Arg141Ser
Coding: c.423G>T
MANE Select: NM_004415
dbSNP: rs771688614
Type: single nucleotide variant
Location: chr6:7559226 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 141: the 'globular 1' region; the 'interaction with mapre1' region; the 'interaction with jup and pkp2' region; a UniProt-annotated variant site (in arvd8; uncertain significance)

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

Disease context

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

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

Similar variants

DSP p.Arg141Lys Uncertain significance ★ ⚠ same residue
DSP p.Arg141Thr 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-arg141ser (accessed [today's date]).

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