Is DSP p.Ile2372= (c.7116C>T) pathogenic?

DSP p.Ile2372= (c.7116C>T) is classified Likely benign in DSP (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-04-01). Ultra-rare (popmax 0.0165%, mid); Associated with arrhythmogenic cardiomyopathy with wooly hair and keratoderma.

What condition is associated with DSP p.Ile2372= (c.7116C>T)?

DSP p.Ile2372= (c.7116C>T) is associated with arrhythmogenic cardiomyopathy with wooly hair and keratoderma, cardiomyopathy, arrhythmogenic right ventricular dysplasia 8 (ClinVar).

How common is DSP p.Ile2372= (c.7116C>T) in the general population?

DSP p.Ile2372= (c.7116C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

How is Carvajal syndrome inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

DSP p.Ile2372=

c.7116C>T · rs185213858 · VCV923373

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

arrhythmogenic cardiomyopathy with wooly hair and keratoderma

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 -8.4	GERP -3.8
Overall
CADD	1.291	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.0092% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00721%

Overall 0.00192% 31/1,614,068 alleles · ultra-rare exomes 26/1,461,820 · genomes 5/152,248 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
African / African-American	0.016%	6,251
Remaining individualsnot grpmax-eligible	0.0144%	6,945
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
Admixed American	0.00333%	30,008
European (non-Finnish)	0.000508%	196,660

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.Ile2372=
Coding: c.7116C>T
MANE Select: NM_004415
dbSNP: rs185213858
Type: single nucleotide variant
Location: chr6:7584378 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2372: 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); an α-helix; the 'binds to telomeres' region; the 'globular 2' region; the '4.5 x 38 aa tandem repeats (domain b)' 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

arrhythmogenic cardiomyopathy with wooly hair and keratoderma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiomyopathy arrhythmogenic right ventricular dysplasia 8

For Carvajal syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Childhood, Infancy, Neonatal

Similar variants

DSP p.Ile2372fs Likely pathogenic ★ same residue
DSP p.Ile2372Met 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-ile2372 (accessed [today's date]).

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