Is DSP p.Ser2815Ile (c.8444G>T) pathogenic?

DSP p.Ser2815Ile (c.8444G>T) is classified Uncertain significance in DSP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-22). AlphaMissense: likely pathogenic (0.9525); Very rare (popmax 0.00133%, afr); Associated with Cardiovascular phenotype.

What condition is associated with DSP p.Ser2815Ile (c.8444G>T)?

DSP p.Ser2815Ile (c.8444G>T) is associated with Cardiovascular phenotype (ClinVar).

How common is DSP p.Ser2815Ile (c.8444G>T) in the general population?

DSP p.Ser2815Ile (c.8444G>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about DSP p.Ser2815Ile (c.8444G>T)?

AlphaMissense predicts likely pathogenic (score 0.9525) — an in-silico prediction, not a clinical call.

DSP p.Ser2815Ile

c.8444G>T · rs2533951848 · VCV3224257

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9525 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.9525	likely pathogenic · top 10% in DSP
REVEL	0.564	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	27.4	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

Grpmax group 0.00133% African / African-American · 1/75,018 alleles

Overall 6.84e-05% 1/1,461,534 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.Ser2815Ile
Coding: c.8444G>T
MANE Select: NM_004415
dbSNP: rs2533951848
Type: single nucleotide variant
Location: chr6:7585706 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2815: 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); the 'binds to telomeres' region; the 'globular 2' region; the '4.5 x 38 aa tandem repeats (domain c)' region; the 'disordered' region; a modified residue (phosphoserine); 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

Similar variants

DSP p.Ser2815= Likely benign ★★ same residue
DSP c.778-2A>G Likely pathogenic ★★ same condition
DSP p.Arg1267Ter Pathogenic/Likely pathogenic ★★ same condition
DSP p.Arg160Ter Pathogenic/Likely pathogenic ★★ same condition
DSP p.Arg1738Ter Pathogenic ★★ same condition
DSP p.Arg270Ter Pathogenic/Likely pathogenic ★★ same condition
DSP p.Arg425Ter Pathogenic/Likely pathogenic ★★ same condition
DSP p.Arg941Ter 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-ser2815ile (accessed [today's date]).

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