Is DSE p.Ala528Thr (c.1582G>A) pathogenic?

DSE p.Ala528Thr (c.1582G>A) is classified Uncertain significance in DSE (ClinVar, Single submitter, 1 submitter; last evaluated 2020-10-20). AlphaMissense: likely benign (0.1222); Very rare (popmax 0.000254%, nfe).

How common is DSE p.Ala528Thr (c.1582G>A) in the general population?

DSE p.Ala528Thr (c.1582G>A) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about DSE p.Ala528Thr (c.1582G>A)?

AlphaMissense predicts likely benign (score 0.1222) — an in-silico prediction, not a clinical call.

DSE p.Ala528Thr

c.1582G>A · rs773958566 · VCV1205788

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1222 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1222	likely benign
REVEL	0.415	indeterminate
SaProt	LLR -10.55	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
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 0.73	unconstrained · MANE · 624 bp · p 1.5e-05 · regional, not allelic
Overall
CADD	24.5	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 0.000254% European (non-Finnish) · 3/1,180,022 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.00197% 3/152,154 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: DSE
Protein: p.Ala528Thr
Coding: c.1582G>A
MANE Select: NM_013352
dbSNP: rs773958566
Type: single nucleotide variant
Location: chr6:116436050 (GRCh38)
Gene constraint: LOEUF 0.563 · pLI 0.06 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.59 · 1 PDB
Residue 528: a β-strand

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-ala528thr (accessed [today's date]).

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