Is DSE p.Ile796Thr (c.2387T>C) pathogenic?

DSE p.Ile796Thr (c.2387T>C) is classified Uncertain significance in DSE (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-27). AlphaMissense: ambiguous (0.4802); Very rare (popmax 0.0011%, sas).

How common is DSE p.Ile796Thr (c.2387T>C) in the general population?

DSE p.Ile796Thr (c.2387T>C) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about DSE p.Ile796Thr (c.2387T>C)?

AlphaMissense predicts ambiguous (score 0.4802) — an in-silico prediction, not a clinical call.

DSE p.Ile796Thr

c.2387T>C · rs2482307341 · VCV2577573

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4802 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4802	ambiguous
REVEL	0.221	benign-leaning
SaProt	LLR -5.37	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 870 bp · p 0.076 · regional, not allelic
Overall
CADD	23.2	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

Grpmax group 0.0011% South Asian · 1/91,068 alleles

Overall 0.000137% 2/1,461,840 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,068
European (non-Finnish)	8.47e-05%	1,179,999

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.Ile796Thr
Coding: c.2387T>C
MANE Select: NM_013352
dbSNP: rs2482307341
Type: single nucleotide variant
Location: chr6:116436855 (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 p.Ile796Val Uncertain significance ★★ ⚠ same residue
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

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-ile796thr (accessed [today's date]).

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