Is DSP p.Ala2750Gly (c.8249C>G) pathogenic?

DSP p.Ala2750Gly (c.8249C>G) is classified Uncertain significance in DSP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-10). AlphaMissense: likely benign (0.2102); Absent from gnomAD v4.1; Associated with cardiomyopathy.

What condition is associated with DSP p.Ala2750Gly (c.8249C>G)?

DSP p.Ala2750Gly (c.8249C>G) is associated with cardiomyopathy (ClinVar).

How common is DSP p.Ala2750Gly (c.8249C>G) in the general population?

DSP p.Ala2750Gly (c.8249C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DSP p.Ala2750Gly (c.8249C>G)?

AlphaMissense predicts likely benign (score 0.2102) — an in-silico prediction, not a clinical call.

DSP p.Ala2750Gly

c.8249C>G · rs2533950497 · VCV2775380

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2102 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Conditions

cardiomyopathy

Computational evidence

Protein change
AlphaMissense	0.2102	likely benign
REVEL	0.925	moderately pathogenic-leaning
⇒ REVEL calls this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 1,308 bp · p 0.26 · regional, not allelic
Overall
CADD	25.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DSP
Protein: p.Ala2750Gly
Coding: c.8249C>G
MANE Select: NM_004415
dbSNP: rs2533950497
Type: single nucleotide variant
Location: chr6:7585511 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2750: 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); a UniProt-annotated variant site (in ebla; uncertain significance); a UniProt-annotated variant site (in dcwhk; uncertain significance); an α-helix; the 'binds to telomeres' region; the 'globular 2' region; the '4.5 x 38 aa tandem repeats (domain c)' 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

Similar variants

DSP p.Ala2750Val Uncertain significance ★★ ⚠ same residue
DSP c.2130+1G>A Pathogenic/Likely pathogenic ★★ same condition
DSP c.2437-1G>C Likely pathogenic ★★ same condition
DSP c.273+1G>A Pathogenic/Likely pathogenic ★★ same condition
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

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-ala2750gly (accessed [today's date]).

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