Is DSP p.Met1Val (c.1A>G) pathogenic?

DSP p.Met1Val (c.1A>G) is classified Uncertain significance in DSP (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-11-13). Very rare (popmax 0.00112%, sas); Associated with cardiomyopathy.

What condition is associated with DSP p.Met1Val (c.1A>G)?

DSP p.Met1Val (c.1A>G) is associated with cardiomyopathy, arrhythmogenic cardiomyopathy with wooly hair and keratoderma (ClinVar).

How common is DSP p.Met1Val (c.1A>G) in the general population?

DSP p.Met1Val (c.1A>G) is very rare (popmax 0.00112%, sas) (gnomAD).

DSP p.Met1Val

c.1A>G · rs1131691557 · VCV429736

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

start-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00112%, sas)

Conditions

cardiomyopathy

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function
REVEL	0.468	indeterminate
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 10	GERP 1.4, phastCons 1
Overall
CADD	23.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00112% South Asian · 1/89,356 alleles

Overall 6.4e-05% 1/1,562,246 alleles · very rare exomes 1/1,457,608 · genomes 0/104,638 · 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.Met1Val
Coding: c.1A>G
MANE Select: NM_004415
dbSNP: rs1131691557
Type: single nucleotide variant
Location: chr6:7541916 (GRCh38)

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

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-met1val (accessed [today's date]).

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