Is DSE p.Ala883Ser (c.2647G>T) pathogenic?

DSE p.Ala883Ser (c.2647G>T) is classified Uncertain significance in DSE (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-12). AlphaMissense: likely benign (0.0693); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with DSE p.Ala883Ser (c.2647G>T)?

DSE p.Ala883Ser (c.2647G>T) is associated with Inborn genetic diseases (ClinVar).

How common is DSE p.Ala883Ser (c.2647G>T) in the general population?

DSE p.Ala883Ser (c.2647G>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about DSE p.Ala883Ser (c.2647G>T)?

AlphaMissense predicts likely benign (score 0.0693) — an in-silico prediction, not a clinical call.

DSE p.Ala883Ser

c.2647G>T · rs1175622871 · VCV2243642

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0693 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0693	likely benign
REVEL	0.022	moderately benign-leaning
SaProt	LLR -5.32	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 1.9	GERP 0.14, phastCons 0.98
Regional constraint	o/e 0.90	unconstrained · MANE · 870 bp · p 0.076 · regional, not allelic
Overall
CADD	13.6	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

Grpmax group 0.00167% Admixed American · 1/60,008 alleles

Overall 0.000205% 3/1,461,846 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,008
Remaining individualsnot grpmax-eligible	0.0016%	62,512
African / African-American	0.00133%	75,024

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: DSE
Protein: p.Ala883Ser
Coding: c.2647G>T
MANE Select: NM_013352
dbSNP: rs1175622871
Type: single nucleotide variant
Location: chr6:116437115 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DSE p.Ala883Thr Uncertain significance ★ ⚠ same residue
DSE p.Ala135Val Uncertain significance ★★ ⚠ same condition
DSE p.Ala584Val Uncertain significance ★★ ⚠ same condition
DSE p.Ala695Thr Uncertain significance ★★ ⚠ same condition
DSE p.Ala910Gly Uncertain significance ★★ ⚠ same condition
DSE p.Arg2Lys Uncertain significance ★★ ⚠ same condition
DSE p.Arg765Gln Uncertain significance ★★ ⚠ same condition
DSE p.Arg815Cys Uncertain significance ★★ ⚠ 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/dse-p-ala883ser (accessed [today's date]).

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