Is DSP p.Asp352fs (c.1054_1059delinsCA) pathogenic?

DSP p.Asp352fs (c.10541059delinsCA) is classified Pathogenic/Likely pathogenic in DSP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-13). Absent from gnomAD; Associated with Cardiovascular phenotype.

What condition is associated with DSP p.Asp352fs (c.1054_1059delinsCA)?

DSP p.Asp352fs (c.1054_1059delinsCA) is associated with Cardiovascular phenotype (ClinVar).

How common is DSP p.Asp352fs (c.1054_1059delinsCA) in the general population?

DSP p.Asp352fs (c.1054_1059delinsCA) is absent from gnomAD (gnomAD).

DSP p.Asp352fs

c.1054_1059delinsCA · rs1064793435 · VCV418788

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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	predicted	premature termination codon in exon 9 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DSP
Protein: p.Asp352fs
Coding: c.1054_1059delinsCA
MANE Select: NM_004415
dbSNP: rs1064793435
Type: Indel
Location: chr6:7567363 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 352: an α-helix; the 'globular 1' region; the 'interaction with mapre1' region; the 'interaction with jup and pkp2' region; the 'interaction with pkp1' region; a UniProt-annotated variant site (in arvd8; uncertain significance); a UniProt-annotated variant site (in dcwhkta; uncertain significance); 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)

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

Similar variants

DSP c.5671_*835+957del4738insAGAACAGTCTT Pathogenic/Likely pathogenic ★★ same condition
DSP p.Asp352Asn Uncertain significance ★★ same residue
DSP p.Met1203_Ser1204delinsIleGly Uncertain significance ★★ same condition
DSP p.Pro2099Ile Uncertain significance ★★ same condition
DSP p.Ser1462Ile Uncertain significance ★★ same condition
DSP p.Val495Phe Uncertain significance ★★ same condition
DSP p.Leu1412fs Pathogenic ★ same condition
DSP p.Ser1801fs 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-asp352fs (accessed [today's date]).

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