Is DSP p.Phe2172fs (c.6516del) pathogenic?

DSP p.Phe2172fs (c.6516del) is classified Pathogenic in DSP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-10-24). Ultra-rare (gnomAD MAF 7.135e-07); Associated with Cardiovascular phenotype.

How common is DSP p.Phe2172fs (c.6516del) in the general population?

DSP p.Phe2172fs (c.6516del) is ultra-rare (gnomAD MAF 7.135e-07) (gnomAD).

DSP p.Phe2172fs

Q: What condition is associated with DSP p.Phe2172fs (c.6516del)?

DSP p.Phe2172fs (c.6516del) is associated with Cardiovascular phenotype, arrhythmogenic cardiomyopathy with wooly hair and keratoderma, arrhythmogenic right ventricular dysplasia 8 (ClinVar).

c.6516del · rs2533941799 · VCV1753982

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (gnomAD MAF 7.135e-07)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	escapes	premature termination codon in the last exon (24 of 24) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.91	GERP -1.9, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

Global frequency 7.13e-05% via dbSNP · ultra-rare

No ancestry breakdown or filtering allele frequency is available for this variant, so BA1/BS1 cannot be assessed from this figure alone.

Variant & gene context

Gene: DSP
Protein: p.Phe2172fs
Coding: c.6516del
MANE Select: NM_004415
dbSNP: rs2533941799
Type: Deletion
Location: chr6:7583776 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2172: 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); the 'binds to telomeres' region; the 'globular 2' region; the '4.5 x 38 aa tandem repeats (domain a)' 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: arrhythmogenic cardiomyopathy with wooly hair and keratoderma arrhythmogenic right ventricular dysplasia 8

Similar variants

DSP p.Phe2172= Likely benign ★★ same residue
DSP c.2131-3_2131del Likely pathogenic ★★ same condition
DSP p.Ala2092fs Pathogenic/Likely pathogenic ★★ same condition
DSP p.Arg1113fs Pathogenic ★★ same condition
DSP p.Arg1173fs Pathogenic ★★ same condition
DSP p.Arg1506fs Pathogenic/Likely pathogenic ★★ same condition
DSP p.Asn1346fs Pathogenic/Likely pathogenic ★★ same condition
DSP p.Asn257fs 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-phe2172fs (accessed [today's date]).

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