Is DSE p.Ile796Val (c.2386A>G) pathogenic?

DSE p.Ile796Val (c.2386A>G) is classified Uncertain significance in DSE (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-11). AlphaMissense: likely benign (0.0744); Ultra-rare (popmax 0.02%, eas); Associated with Inborn genetic diseases.

What condition is associated with DSE p.Ile796Val (c.2386A>G)?

DSE p.Ile796Val (c.2386A>G) is associated with Inborn genetic diseases, Ehlers-Danlos syndrome, musculocontractural type 2 (ClinVar).

How common is DSE p.Ile796Val (c.2386A>G) in the general population?

DSE p.Ile796Val (c.2386A>G) is ultra-rare (popmax 0.02%, eas) (gnomAD).

What do computational predictors say about DSE p.Ile796Val (c.2386A>G)?

AlphaMissense predicts likely benign (score 0.0744) — an in-silico prediction, not a clinical call.

DSE p.Ile796Val

c.2386A>G · rs774012350 · VCV1512592

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0744 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0744	likely benign
REVEL	0.115	moderately benign-leaning
SaProt	LLR -5.77	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 5.4	GERP 2.1, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 870 bp · p 0.076 · regional, not allelic
Overall
CADD	17.69	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 0.02% East Asian · 9/44,900 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00779%

Overall 0.000743% 12/1,614,018 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.02%	4,989
African / African-American	0.00267%	37,460
European (non-Finnish)	8.47e-05%	1,180,006

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.Ile796Val
Coding: c.2386A>G
MANE Select: NM_013352
dbSNP: rs774012350
Type: single nucleotide variant
Location: chr6:116436854 (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

Also linked: Ehlers-Danlos syndrome, musculocontractural type 2

Similar variants

DSE p.Ile796Thr Uncertain significance ★ ⚠ same residue
DSE c.416+1G>A Likely pathogenic ★★ same condition
DSE p.Ala122Thr Uncertain significance ★★ same condition
DSE p.Ala135Val Uncertain significance ★★ ⚠ same condition
DSE p.Ala408Thr Uncertain significance ★★ ⚠ same condition
DSE p.Ala54Val Uncertain significance ★★ ⚠ same condition
DSE p.Ala584Val Uncertain significance ★★ ⚠ same condition
DSE p.Ala688Val 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-ile796val (accessed [today's date]).

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