Is DSP p.Arg1045Gln (c.3134G>A) pathogenic?

DSP p.Arg1045Gln (c.3134G>A) is classified Conflicting classifications of pathogenicity in DSP (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2025-12-03). AlphaMissense: likely benign (0.155); Ultra-rare (popmax 0.0173%, afr); Associated with cardiomyopathy.

How common is DSP p.Arg1045Gln (c.3134G>A) in the general population?

DSP p.Arg1045Gln (c.3134G>A) is ultra-rare (popmax 0.0173%, afr) (gnomAD).

What do computational predictors say about DSP p.Arg1045Gln (c.3134G>A)?

AlphaMissense predicts likely benign (score 0.155) — an in-silico prediction, not a clinical call.

DSP p.Arg1045Gln

Q: What condition is associated with DSP p.Arg1045Gln (c.3134G>A)?

DSP p.Arg1045Gln (c.3134G>A) is associated with cardiomyopathy, arrhythmogenic cardiomyopathy with wooly hair and keratoderma, arrhythmogenic right ventricular dysplasia 8 (ClinVar).

c.3134G>A · rs374263890 · VCV222577

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.155 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0173%, afr)

Conditions

cardiomyopathy

Computational evidence

Protein change
AlphaMissense	0.155	likely benign
REVEL	0.338	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.5, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 12 kb · p 0.0024 · regional, not allelic
Overall
CADD	26.5	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 0.0173% African / African-American · 13/75,046 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00811%

Overall 0.00167% 27/1,614,164 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0173%	5,773
Finnishnot grpmax-eligible	0.00469%	21,337
East Asian	0.00223%	44,876
South Asian	0.0022%	45,539
Admixed American	0.00167%	60,026
European (non-Finnish)	0.000593%	168,577

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.Arg1045Gln
Coding: c.3134G>A
MANE Select: NM_004415
dbSNP: rs374263890
Type: single nucleotide variant
Location: chr6:7579324 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1045: a UniProt-annotated variant site (in arvd8; uncertain significance); a UniProt-annotated variant site (in dcwhkta; uncertain significance); the 'globular 1' 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

cardiomyopathy — 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 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.Arg1045Ter Pathogenic/Likely pathogenic ★★ same residue
DSP p.Arg1045Pro Conflicting classifications of pathogenicity ★ same residue
DSP p.Arg1045_Asp1046delinsGlnAsn 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

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-arg1045gln (accessed [today's date]).

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