Is DSP p.Ala1688Val (c.5063C>T) pathogenic?

DSP p.Ala1688Val (c.5063C>T) is classified Conflicting classifications of pathogenicity in DSP (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-11). AlphaMissense: likely benign (0.0934); Ultra-rare (popmax 0.0329%, mid); Associated with Cardiovascular phenotype.

What condition is associated with DSP p.Ala1688Val (c.5063C>T)?

DSP p.Ala1688Val (c.5063C>T) is associated with Cardiovascular phenotype, cardiomyopathy, arrhythmogenic right ventricular dysplasia 1 (ClinVar).

How common is DSP p.Ala1688Val (c.5063C>T) in the general population?

DSP p.Ala1688Val (c.5063C>T) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

What do computational predictors say about DSP p.Ala1688Val (c.5063C>T)?

AlphaMissense predicts likely benign (score 0.0934) — an in-silico prediction, not a clinical call.

DSP p.Ala1688Val

c.5063C>T · rs372288373 · VCV188467

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0934 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0934	likely benign
REVEL	0.125	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 0.59	GERP 0.91, phastCons 0.089
Regional constraint	o/e 0.93	unconstrained · MANE · 12 kb · p 0.0024 · regional, not allelic
Overall
CADD	18.42	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 0.0329% Middle Eastern · 2/6,082 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00241%

Overall 0.0026% 42/1,613,854 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,041
Admixed American	0.00667%	14,997
Remaining individualsnot grpmax-eligible	0.0032%	31,241
European (non-Finnish)	0.00254%	39,334
East Asian	0.00223%	44,888
South Asian	0.0022%	45,545
African / African-American	0.00134%	74,860

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.Ala1688Val
Coding: c.5063C>T
MANE Select: NM_004415
dbSNP: rs372288373
Type: single nucleotide variant
Location: chr6:7581253 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1688: 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); 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 right ventricular dysplasia 1 arrhythmogenic cardiomyopathy with wooly hair and keratoderma arrhythmogenic right ventricular dysplasia 8

Similar variants

DSP p.Ala1688Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
DSP p.Ala1688= Likely benign ★ same residue
DSP p.Ala1688fs 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

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-ala1688val (accessed [today's date]).

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