Is DSE p.Val764Asp (c.2291T>A) pathogenic?

DSE p.Val764Asp (c.2291T>A) is classified Uncertain significance in DSE (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-03). AlphaMissense: likely pathogenic (0.9119); Very rare (popmax 0.00935%, afr); Associated with Inborn genetic diseases.

What condition is associated with DSE p.Val764Asp (c.2291T>A)?

DSE p.Val764Asp (c.2291T>A) is associated with Inborn genetic diseases (ClinVar).

How common is DSE p.Val764Asp (c.2291T>A) in the general population?

DSE p.Val764Asp (c.2291T>A) is very rare (popmax 0.00935%, afr) (gnomAD).

What do computational predictors say about DSE p.Val764Asp (c.2291T>A)?

AlphaMissense predicts likely pathogenic (score 0.9119) — an in-silico prediction, not a clinical call.

DSE p.Val764Asp

c.2291T>A · rs762654146 · VCV2264598

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9119 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00935%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9119	likely pathogenic
REVEL	0.463	indeterminate
SaProt	LLR -4.97	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 2.1, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 870 bp · p 0.076 · regional, not allelic
Overall
CADD	25.9	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 0.00935% African / African-American · 7/74,896 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.000434% 7/1,613,958 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.Val764Asp
Coding: c.2291T>A
MANE Select: NM_013352
dbSNP: rs762654146
Type: single nucleotide variant
Location: chr6:116436759 (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 764: an α-helix

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.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
DSE p.Arg97His 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-val764asp (accessed [today's date]).

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