Is DSP p.Asn4Lys (c.12C>G) pathogenic?

DSP p.Asn4Lys (c.12C>G) is classified Benign/Likely benign in DSP (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-04). AlphaMissense: ambiguous (0.4595); Low-frequency (popmax 2.93%, amr); Associated with Cardiovascular phenotype.

What condition is associated with DSP p.Asn4Lys (c.12C>G)?

DSP p.Asn4Lys (c.12C>G) is associated with Cardiovascular phenotype, cardiomyopathy, arrhythmogenic cardiomyopathy with wooly hair and keratoderma (ClinVar).

How common is DSP p.Asn4Lys (c.12C>G) in the general population?

DSP p.Asn4Lys (c.12C>G) is low-frequency (popmax 2.93%, amr) (gnomAD).

What do computational predictors say about DSP p.Asn4Lys (c.12C>G)?

AlphaMissense predicts ambiguous (score 0.4595) — an in-silico prediction, not a clinical call.

DSP p.Asn4Lys

c.12C>G · rs368802003 · VCV44858

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

AlphaMissense

ambiguous

0.4595 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.93%, amr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.4595	ambiguous
REVEL	0.113	moderately benign-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3.3	GERP 0.22, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 29 kb · p 0.14 · regional, not allelic
Overall
CADD	22.3	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 2.93% Admixed American · 1,746/59,574 alleles

Filtering AF 2.82% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.77%

Overall 0.114% 1,832/1,608,092 alleles · low-frequency

Ancestry group	Frequency	1 in
Admixed Americangrpmax	2.93%	34
Remaining individualsnot grpmax-eligible	0.0674%	1,483
African / African-American	0.0269%	3,713
South Asian	0.0199%	5,025
European (non-Finnish)	0.000509%	196,411

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.Asn4Lys
Coding: c.12C>G
dbSNP: rs368802003
Type: single nucleotide variant
Location: chr6:7541927 (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 lethal acantholytic epidermolysis bullosa woolly hair-skin fragility syndrome

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-asn4lys (accessed [today's date]).

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