Is DSP p.Ala562Val (c.1685C>T) pathogenic?

DSP p.Ala562Val (c.1685C>T) is classified Uncertain significance in DSP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-05). AlphaMissense: likely benign (0.31); Very rare (popmax 0.00446%, eas); Associated with cardiomyopathy.

What condition is associated with DSP p.Ala562Val (c.1685C>T)?

DSP p.Ala562Val (c.1685C>T) is associated with cardiomyopathy (ClinVar).

How common is DSP p.Ala562Val (c.1685C>T) in the general population?

DSP p.Ala562Val (c.1685C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about DSP p.Ala562Val (c.1685C>T)?

AlphaMissense predicts likely benign (score 0.31) — an in-silico prediction, not a clinical call.

DSP p.Ala562Val

c.1685C>T · rs767605301 · VCV920103

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.31 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cardiomyopathy

Computational evidence

Protein change
AlphaMissense	0.31	likely benign
REVEL	0.22	benign-leaning
SaProt	LLR -8.62	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 1,387 bp · p 1.5e-05 · regional, not allelic
Overall
CADD	25.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,888 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000124% 2/1,613,192 alleles · very rare exomes 1/1,461,034 · genomes 1/152,158 · joint denominator

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.Ala562Val
Coding: c.1685C>T
MANE Select: NM_004415
dbSNP: rs767605301
Type: single nucleotide variant
Location: chr6:7570547 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 562: 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); 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

Similar variants

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DSP c.939+1G>A Pathogenic/Likely pathogenic ★★ same condition
DSP p.Arg1113Ter Pathogenic/Likely pathogenic ★★ same condition
DSP p.Arg1267Ter Pathogenic/Likely pathogenic ★★ same condition
DSP p.Arg1269Ter Pathogenic/Likely pathogenic ★★ same condition
DSP p.Arg1400Ter Pathogenic/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-ala562val (accessed [today's date]).

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