Is DSP p.Arg150Gln (c.449G>A) pathogenic?

DSP p.Arg150Gln (c.449G>A) is classified Conflicting classifications of pathogenicity in DSP (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-08-24). AlphaMissense: ambiguous (0.4899); Very rare (popmax 0.00549%, sas); Associated with arrhythmogenic cardiomyopathy with wooly hair and keratoderma.

What condition is associated with DSP p.Arg150Gln (c.449G>A)?

DSP p.Arg150Gln (c.449G>A) is associated with arrhythmogenic cardiomyopathy with wooly hair and keratoderma, cardiomyopathy, arrhythmogenic right ventricular dysplasia 8 (ClinVar).

How common is DSP p.Arg150Gln (c.449G>A) in the general population?

DSP p.Arg150Gln (c.449G>A) is very rare (popmax 0.00549%, sas) (gnomAD).

How is Carvajal syndrome inherited?

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

What do computational predictors say about DSP p.Arg150Gln (c.449G>A)?

AlphaMissense predicts ambiguous (score 0.4899) — an in-silico prediction, not a clinical call.

DSP p.Arg150Gln

c.449G>A · rs587782940 · VCV155786

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

ambiguous

0.4899 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Conditions

arrhythmogenic cardiomyopathy with wooly hair and keratoderma

Computational evidence

Protein change
AlphaMissense	0.4899	ambiguous
REVEL	0.283	benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.35 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 29 kb · p 0.14 · regional, not allelic
Overall
CADD	29.6	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 0.00549% South Asian · 5/91,080 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.00112% 18/1,613,870 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,216
Remaining individualsnot grpmax-eligible	0.0048%	20,822
African / African-American	0.00401%	24,969
European (non-Finnish)	0.000593%	168,576

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.Arg150Gln
Coding: c.449G>A
MANE Select: NM_004415
dbSNP: rs587782940
Type: single nucleotide variant
Location: chr6:7559252 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 150: the 'globular 1' region; the 'interaction with mapre1' region; the 'interaction with jup and pkp2' region; a UniProt-annotated variant site (in arvd8; uncertain significance); a UniProt-annotated variant site (in dcwhkta; uncertain significance)

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 lethal acantholytic epidermolysis bullosa keratosis palmoplantaris striata 2 cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis woolly hair-skin fragility syndrome

For Carvajal syndrome (Orphanet):

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

Similar variants

DSP p.Arg150Ter Pathogenic ★★ same residue
DSP p.Arg150Leu 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-arg150gln (accessed [today's date]).

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