Is DSP p.Gln1861Pro (c.5582A>C) pathogenic?

DSP p.Gln1861Pro (c.5582A>C) is classified Uncertain significance in DSP (ClinVar, Single submitter, 1 submitter; last evaluated 2014-04-04). AlphaMissense: likely pathogenic (0.897); Absent from gnomAD v4.1.

How common is DSP p.Gln1861Pro (c.5582A>C) in the general population?

DSP p.Gln1861Pro (c.5582A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DSP p.Gln1861Pro (c.5582A>C)?

AlphaMissense predicts likely pathogenic (score 0.897) — an in-silico prediction, not a clinical call.

DSP p.Gln1861Pro

c.5582A>C · rs794728125 · VCV199891

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.897 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.897	likely pathogenic
REVEL	0.197	benign-leaning
⇒ AlphaMissense calls this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.4, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 12 kb · p 0.0024 · regional, not allelic
Overall
CADD	22.4	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.Gln1861Pro
Coding: c.5582A>C
MANE Select: NM_004415
dbSNP: rs794728125
Type: single nucleotide variant
Location: chr6:7582844 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1861: 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); 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 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
DSP c.2130+1G>A Pathogenic/Likely pathogenic ★★ same type
DSP c.2297+1G>A Likely pathogenic ★★ same type
DSP c.2298-1G>C Likely pathogenic ★★ same type
DSP c.2298-2A>C Pathogenic/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-gln1861pro (accessed [today's date]).

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