Is DSP p.Asp1248Val (c.3743A>T) pathogenic?

DSP p.Asp1248Val (c.3743A>T) is classified Uncertain significance in DSP (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-01). AlphaMissense: ambiguous (0.3494); Absent from gnomAD v4.1.

How common is DSP p.Asp1248Val (c.3743A>T) in the general population?

DSP p.Asp1248Val (c.3743A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DSP p.Asp1248Val (c.3743A>T)?

AlphaMissense predicts ambiguous (score 0.3494) — an in-silico prediction, not a clinical call.

DSP p.Asp1248Val

c.3743A>T · VCV4874593

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3494 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.3494	ambiguous
REVEL	0.581	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.1	GERP 0.5, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 12 kb · p 0.0024 · regional, not allelic
Overall
CADD	24.2	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.Asp1248Val
Coding: c.3743A>T
MANE Select: NM_004415
Type: single nucleotide variant
Location: chr6:7579933 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1248: a UniProt-annotated variant site (in arvd8; uncertain significance); a UniProt-annotated variant site (in dcwhkta; uncertain significance); the 'central fibrous rod domain' region; the 'binds to telomeres' 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

Similar variants

DSP p.Asp1248Asn Uncertain significance ★★ same residue
DSP p.Asp1248His Uncertain significance ★★ same residue
DSP p.Asp1248Ala Conflicting classifications of pathogenicity ★ same residue
DSP p.Asp1248fs Pathogenic ★★ same residue
DSP c.1141-2A>G Likely pathogenic ★★ same type
DSP c.1141-2A>T Likely pathogenic ★★ same type
DSP c.1266+2T>C Likely pathogenic ★★ same type
DSP c.1574+1G>A Likely pathogenic ★★ same type

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-asp1248val (accessed [today's date]).

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