Is DSE p.Asp820Gly (c.2459A>G) pathogenic?

DSE p.Asp820Gly (c.2459A>G) is classified Uncertain significance in DSE (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-03). AlphaMissense: likely benign (0.1877); Absent from gnomAD v4.1.

How common is DSE p.Asp820Gly (c.2459A>G) in the general population?

DSE p.Asp820Gly (c.2459A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DSE p.Asp820Gly (c.2459A>G)?

AlphaMissense predicts likely benign (score 0.1877) — an in-silico prediction, not a clinical call.

DSE p.Asp820Gly

c.2459A>G · VCV4848095

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1877 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1877	likely benign
REVEL	0.271	benign-leaning
SaProt	LLR -7.33	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 2.1, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 870 bp · p 0.076 · regional, not allelic
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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: DSE
Protein: p.Asp820Gly
Coding: c.2459A>G
MANE Select: NM_013352
Type: single nucleotide variant
Location: chr6:116436927 (GRCh38)
Gene constraint: LOEUF 0.563 · pLI 0.06 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.59 · 1 PDB

Full DSE gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DSE c.416+1G>A Likely pathogenic ★★ same type
DSE p.Ala122Thr Uncertain significance ★★ ⚠ same type
DSE p.Ala135Val Uncertain significance ★★ ⚠ same type
DSE p.Ala408Thr Uncertain significance ★★ ⚠ same type
DSE p.Ala54Val Uncertain significance ★★ ⚠ same type
DSE p.Ala584Val Uncertain significance ★★ ⚠ same type
DSE p.Ala688Val Uncertain significance ★★ ⚠ same type
DSE p.Ala695Thr Uncertain significance ★★ ⚠ 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/dse-p-asp820gly (accessed [today's date]).

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