Is DSP p.Tyr42= (c.126T>C) pathogenic?

DSP p.Tyr42= (c.126T>C) is classified Benign in DSP (ClinVar, Multiple submitters, 17 submitters; last evaluated 2026-02-04). Common (popmax 10.3%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Cardiovascular phenotype.

What condition is associated with DSP p.Tyr42= (c.126T>C)?

DSP p.Tyr42= (c.126T>C) is associated with Cardiovascular phenotype, cardiomyopathy, arrhythmogenic cardiomyopathy with wooly hair and keratoderma (ClinVar).

DSP p.Tyr42=

Q: How common is DSP p.Tyr42= (c.126T>C) in the general population?

DSP p.Tyr42= (c.126T>C) is common (popmax 10.3%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.126T>C · rs36087964 · VCV44855

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 17 submitters

gnomAD v4.1

Common

common (popmax 10.3%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -0.95, phastCons 1
Overall
CADD	11.96	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 10.3% African / African-American · 7,643/74,078 alleles

Filtering AF 10.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 10%

Overall 5.7% 89,776/1,575,704 alleles · common exomes 79,432/1,423,620 · genomes 10,344/152,084 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	18.6%	5
Ashkenazi Jewishnot grpmax-eligible	10.8%	9
African / African-Americangrpmax	10.3%	10
Middle Eastern	9.16%	11
Remaining individualsnot grpmax-eligible	6.39%	16
Finnishnot grpmax-eligible	6.08%	16
European (non-Finnish)	5.4%	19
South Asian	4.92%	20
East Asian	3.98%	25
Admixed American	3.9%	26

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Tyr42=
Coding: c.126T>C
MANE Select: NM_004415
dbSNP: rs36087964
Type: single nucleotide variant
Location: chr6:7542041 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 42: the 'globular 1' region; the 'interaction with mapre1' region; the 'interaction with jup and pkp2' region

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.Tyr42Cys Uncertain significance ★★ ⚠ same residue
DSP p.Tyr42Ter Likely pathogenic ★ 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-tyr42 (accessed [today's date]).

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