Is DES p.Asn342= (c.1026C>T) pathogenic?

DES p.Asn342= (c.1026C>T) is classified Benign/Likely benign in DES (ClinVar, Multiple submitters, 17 submitters; last evaluated 2026-02-03). Common (popmax 6.93%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Cardiovascular phenotype.

What condition is associated with DES p.Asn342= (c.1026C>T)?

DES p.Asn342= (c.1026C>T) is associated with Cardiovascular phenotype, cardiomyopathy, neurogenic scapuloperoneal syndrome, Kaeser type (ClinVar).

DES p.Asn342=

Q: How common is DES p.Asn342= (c.1026C>T) in the general population?

DES p.Asn342= (c.1026C>T) is common (popmax 6.93%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1026C>T · rs61731508 · VCV44243

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 17 submitters

gnomAD v4.1

Common

common (popmax 6.93%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.85 · evaluated, not missing
Constraint at this position
Conservation	phyloP -13	GERP -3.7
Overall
CADD	0.16	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.93% African / African-American · 5,196/74,986 alleles

Filtering AF 6.77% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.71%

Overall 0.374% 6,042/1,614,016 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.93%	14
Remaining individualsnot grpmax-eligible	0.541%	185
Admixed American	0.518%	193
Middle Eastern	0.379%	264
South Asian	0.0253%	3,960
Ashkenazi Jewishnot grpmax-eligible	0.0236%	4,229
European (non-Finnish)	0.012%	8,310
East Asian	0.00446%	22,440

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.Asn342=
Coding: c.1026C>T
MANE Select: NM_001927
dbSNP: rs61731508
Type: single nucleotide variant
Location: chr2:219421342 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73
Residue 342: the 'coil 2b' region; the if rod domain; a UniProt-annotated variant site (in mfm1; unable to form a filamentous network; abolishes binding to mtm1); 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

Also linked: cardiomyopathy neurogenic scapuloperoneal syndrome, Kaeser type myofibrillar myopathy 1 dilated cardiomyopathy 1I

Similar variants

DES p.Asn342Asp Pathogenic ★ same residue
DES c.1289-2A>G Pathogenic/Likely pathogenic ★★ same condition
DES c.579-2A>C Likely pathogenic ★★ same condition
DES c.735+1G>A Pathogenic/Likely pathogenic ★★ same condition
DES c.735+1G>C Pathogenic/Likely pathogenic ★★ same condition
DES c.735+3A>G Pathogenic ★★ same condition
DES p.Ala120Pro Pathogenic/Likely pathogenic ★★ same condition
DES p.Ala285Val Likely pathogenic ★★ 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-asn342 (accessed [today's date]).

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