Is DSP p.Ala1279Val (c.3836C>T) pathogenic?

DSP p.Ala1279Val (c.3836C>T) is classified Conflicting classifications of pathogenicity in DSP (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-04-29). AlphaMissense: ambiguous (0.3639); Very rare (popmax 0.00924%, nfe); Associated with cardiomyopathy.

How common is DSP p.Ala1279Val (c.3836C>T) in the general population?

DSP p.Ala1279Val (c.3836C>T) is very rare (popmax 0.00924%, nfe) (gnomAD).

What do computational predictors say about DSP p.Ala1279Val (c.3836C>T)?

AlphaMissense predicts ambiguous (score 0.3639) — an in-silico prediction, not a clinical call.

DSP p.Ala1279Val

Q: What condition is associated with DSP p.Ala1279Val (c.3836C>T)?

DSP p.Ala1279Val (c.3836C>T) is associated with cardiomyopathy, arrhythmogenic cardiomyopathy with wooly hair and keratoderma, arrhythmogenic right ventricular dysplasia 8 (ClinVar).

c.3836C>T · rs753270443 · VCV418606

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

ambiguous

0.3639 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00924%, nfe)

Conditions

cardiomyopathy

Computational evidence

Protein change
AlphaMissense	0.3639	ambiguous
REVEL	0.377	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 12 kb · p 0.0024 · regional, not allelic
Overall
CADD	23.3	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 0.00924% European (non-Finnish) · 109/1,180,028 alleles

Filtering AF 0.00782% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00727%

Overall 0.00762% 123/1,613,964 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0128%	7,811
European (non-Finnish)grpmax	0.00924%	10,826
African / African-American	0.00534%	18,724
East Asian	0.00223%	44,890
Admixed American	0.00167%	60,002

Remaining individuals 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.Ala1279Val
Coding: c.3836C>T
MANE Select: NM_004415
dbSNP: rs753270443
Type: single nucleotide variant
Location: chr6:7580026 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1279: a UniProt-annotated variant site (in arvd8; uncertain significance); a UniProt-annotated variant site (in dcwhkta; uncertain significance); 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

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.Ala1279Thr Uncertain significance ★★ same residue
DSP p.Ala1279Ser Conflicting classifications of pathogenicity ★ 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-ala1279val (accessed [today's date]).

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