Is DSP p.Arg1738Gln (c.5213G>A) pathogenic?

DSP p.Arg1738Gln (c.5213G>A) is classified Benign in DSP (ClinVar, Multiple submitters, 19 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0916); Common (popmax 33.2%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Cardiovascular phenotype.

What condition is associated with DSP p.Arg1738Gln (c.5213G>A)?

DSP p.Arg1738Gln (c.5213G>A) is associated with Cardiovascular phenotype, cardiomyopathy, arrhythmogenic cardiomyopathy with wooly hair and keratoderma (ClinVar).

What do computational predictors say about DSP p.Arg1738Gln (c.5213G>A)?

AlphaMissense predicts likely benign (score 0.0916) — an in-silico prediction, not a clinical call.

DSP p.Arg1738Gln

Q: How common is DSP p.Arg1738Gln (c.5213G>A) in the general population?

DSP p.Arg1738Gln (c.5213G>A) is common (popmax 33.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.5213G>A · rs6929069 · VCV44925

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 19 submitters

AlphaMissense

likely benign

0.0916 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 33.2%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0916	likely benign
REVEL	0.066	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP 0.86, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 12 kb · p 0.0024 · regional, not allelic
Overall
CADD	15.21	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 33.2% African / African-American · 24,860/74,852 alleles

Filtering AF 32.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 32.7%

Overall 15.2% 245,157/1,613,616 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	33.2%	3
South Asian	23.4%	4
Middle Eastern	19.1%	5
Admixed American	19%	5
East Asian	18.6%	5
Finnishnot grpmax-eligible	17.3%	6
Remaining individualsnot grpmax-eligible	16.3%	6
Ashkenazi Jewishnot grpmax-eligible	15.9%	6
European (non-Finnish)	12.9%	8
Amishnot grpmax-eligible	6.7%	15

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.Arg1738Gln
Coding: c.5213G>A
MANE Select: NM_004415
dbSNP: rs6929069
Type: single nucleotide variant
Location: chr6:7581403 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1738: 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); 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 woolly hair-skin fragility syndrome

Similar variants

DSP p.Arg1738Ter Pathogenic ★★ same residue
DSP p.Arg1738Gly Uncertain significance ★ ⚠ same residue
DSP p.Arg1738= 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

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-arg1738gln (accessed [today's date]).

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