Is DES p.Asn366Asp (c.1096A>G) pathogenic?

DES p.Asn366Asp (c.1096A>G) is classified Uncertain significance in DES (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-27). AlphaMissense: likely benign (0.2913); Very rare (popmax 8.47e-05%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with DES p.Asn366Asp (c.1096A>G)?

DES p.Asn366Asp (c.1096A>G) is associated with Cardiovascular phenotype (ClinVar).

How common is DES p.Asn366Asp (c.1096A>G) in the general population?

DES p.Asn366Asp (c.1096A>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about DES p.Asn366Asp (c.1096A>G)?

AlphaMissense predicts likely benign (score 0.2913) — an in-silico prediction, not a clinical call.

DES p.Asn366Asp

c.1096A>G · rs2545254946 · VCV1790633

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2913 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.2913	likely benign
REVEL	0.425	indeterminate
SaProt	LLR -10.55	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7	GERP 0.88, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 7,524 bp · p 0.05 · regional, not allelic
Overall
CADD	24.9	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 8.47e-05% European (non-Finnish) · 1/1,180,008 alleles

Overall 6.2e-05% 1/1,614,090 alleles · very rare exomes 1/1,461,844 · genomes 0/152,246 · joint denominator

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: DES
Protein: p.Asn366Asp
Coding: c.1096A>G
MANE Select: NM_001927
dbSNP: rs2545254946
Type: single nucleotide variant
Location: chr2:219421412 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73
Residue 366: the 'coil 2b' region; the if rod domain; a UniProt-annotated variant site (in mfm1); the 'interaction with neb' region

Full DES gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DES p.Asn366Ser Uncertain significance ★★ ⚠ same residue
DES p.Arg212Ter Pathogenic/Likely pathogenic ★★ same condition
DES p.Arg454Trp Pathogenic/Likely pathogenic ★★ same condition
DES p.Glu401Asp Pathogenic/Likely pathogenic ★★ same condition
DES c.1245-3T>G Uncertain significance ★★ same condition
DES c.639+4A>G Uncertain significance ★★ same condition
DES p.Ala135Gly Uncertain significance ★★ ⚠ same condition
DES p.Ala137Val 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/des-p-asn366asp (accessed [today's date]).

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