Is DSP p.Ala2710Ser (c.8128G>T) pathogenic?

DSP p.Ala2710Ser (c.8128G>T) is classified Uncertain significance in DSP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-29). AlphaMissense: likely benign (0.1448); Very rare (popmax 0.000847%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with DSP p.Ala2710Ser (c.8128G>T)?

DSP p.Ala2710Ser (c.8128G>T) is associated with Cardiovascular phenotype, cardiomyopathy (ClinVar).

How common is DSP p.Ala2710Ser (c.8128G>T) in the general population?

DSP p.Ala2710Ser (c.8128G>T) is very rare (popmax 0.000847%, nfe) (gnomAD).

What do computational predictors say about DSP p.Ala2710Ser (c.8128G>T)?

AlphaMissense predicts likely benign (score 0.1448) — an in-silico prediction, not a clinical call.

DSP p.Ala2710Ser

c.8128G>T · rs1561705003 · VCV666382

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1448 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000847%, nfe)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.1448	likely benign
REVEL	0.297	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 1,308 bp · p 0.26 · regional, not allelic
Overall
CADD	25.1	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 0.000847% European (non-Finnish) · 10/1,180,008 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000312%

Overall 0.000684% 10/1,461,858 alleles · very rare

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.Ala2710Ser
Coding: c.8128G>T
MANE Select: NM_004415
dbSNP: rs1561705003
Type: single nucleotide variant
Location: chr6:7585390 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2710: 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

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiomyopathy

Similar variants

DSP p.Ala2710= Likely benign ★★ same residue
DSP p.Ala2710Glu Uncertain significance ★ same residue
DSP p.Ala2710Thr 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.778-2A>G Likely pathogenic ★★ same condition
DSP c.939+1G>A 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-ala2710ser (accessed [today's date]).

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