Is DSE p.Leu778Val (c.2332C>G) pathogenic?

DSE p.Leu778Val (c.2332C>G) is classified Uncertain significance in DSE (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-19). AlphaMissense: ambiguous (0.489); Very rare (popmax 0.00267%, afr); Associated with Inborn genetic diseases.

What condition is associated with DSE p.Leu778Val (c.2332C>G)?

DSE p.Leu778Val (c.2332C>G) is associated with Inborn genetic diseases (ClinVar).

How common is DSE p.Leu778Val (c.2332C>G) in the general population?

DSE p.Leu778Val (c.2332C>G) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about DSE p.Leu778Val (c.2332C>G)?

AlphaMissense predicts ambiguous (score 0.489) — an in-silico prediction, not a clinical call.

DSE p.Leu778Val

c.2332C>G · rs1355449404 · VCV2368567

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.489 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.489	ambiguous
REVEL	0.205	benign-leaning
SaProt	LLR -7.94	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 4	GERP 2.1, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 870 bp · p 0.076 · regional, not allelic
Overall
CADD	24.1	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 0.00267% African / African-American · 2/74,902 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,614,000 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.Leu778Val
Coding: c.2332C>G
MANE Select: NM_013352
dbSNP: rs1355449404
Type: single nucleotide variant
Location: chr6:116436800 (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.Leu778= Benign/Likely benign ★★ 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-leu778val (accessed [today's date]).

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