Is DSP p.Val1440= (c.4320G>A) pathogenic?

DSP p.Val1440= (c.4320G>A) is classified Benign/Likely benign in DSP (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-02). Rare (popmax 0.278%, sas); Associated with Cardiovascular phenotype.

What condition is associated with DSP p.Val1440= (c.4320G>A)?

DSP p.Val1440= (c.4320G>A) is associated with Cardiovascular phenotype, cardiomyopathy, arrhythmogenic cardiomyopathy with wooly hair and keratoderma (ClinVar).

How common is DSP p.Val1440= (c.4320G>A) in the general population?

DSP p.Val1440= (c.4320G>A) is rare (popmax 0.278%, sas) (gnomAD).

DSP p.Val1440=

c.4320G>A · rs571103583 · VCV413260

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

rare (popmax 0.278%, 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 1.7	GERP 1.6, phastCons 0.27
Overall
CADD	5.268	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.278% South Asian · 253/91,064 alleles

Filtering AF 0.25% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.239%

Overall 0.0199% 321/1,614,158 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.278%	360
Remaining individualsnot grpmax-eligible	0.0464%	2,155
Middle Eastern	0.033%	3,031
African / African-American	0.0107%	9,379
European (non-Finnish)	0.00237%	42,144
East Asian	0.00223%	44,878

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.Val1440=
Coding: c.4320G>A
MANE Select: NM_004415
dbSNP: rs571103583
Type: single nucleotide variant
Location: chr6:7580510 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1440: a UniProt-annotated variant site (in arvd8; uncertain significance); a UniProt-annotated variant site (in dcwhkta; uncertain significance); the 'central fibrous rod domain' region; the 'binds to telomeres' 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

Also linked: cardiomyopathy arrhythmogenic cardiomyopathy with wooly hair and keratoderma arrhythmogenic right ventricular dysplasia 8 lethal acantholytic epidermolysis bullosa keratosis palmoplantaris striata 2 cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis woolly hair-skin fragility syndrome

Similar variants

DSP p.Val1440Gly Uncertain significance ★ ⚠ same residue
DSP p.Val1440Met Likely benign ★ 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-val1440 (accessed [today's date]).

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