Is DES p.Asp264= (c.792C>T) pathogenic?

DES p.Asp264= (c.792C>T) is classified Benign/Likely benign in DES (ClinVar, Multiple submitters, 18 submitters; last evaluated 2026-02-02). Low-frequency (popmax 2.81%, amr); Associated with Cardiovascular phenotype.

What condition is associated with DES p.Asp264= (c.792C>T)?

DES p.Asp264= (c.792C>T) is associated with Cardiovascular phenotype, cardiomyopathy, neurogenic scapuloperoneal syndrome, Kaeser type (ClinVar).

How common is DES p.Asp264= (c.792C>T) in the general population?

DES p.Asp264= (c.792C>T) is low-frequency (popmax 2.81%, amr) (gnomAD).

DES p.Asp264=

c.792C>T · rs150370918 · VCV44271

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 18 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.81%, amr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.42	GERP -0.4, phastCons 0.98
Overall
CADD	11.12	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.81% Admixed American · 1,685/60,008 alleles

Filtering AF 2.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.65%

Overall 0.124% 2,008/1,613,928 alleles · low-frequency

Ancestry group	Frequency	1 in
Admixed Americangrpmax	2.81%	36
Remaining individualsnot grpmax-eligible	0.117%	856
East Asian	0.0691%	1,447
African / African-American	0.0587%	1,705
Ashkenazi Jewishnot grpmax-eligible	0.054%	1,851
Middle Eastern	0.033%	3,031
European (non-Finnish)	0.0131%	7,662
South Asian	0.00329%	30,357

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.Asp264=
Coding: c.792C>T
MANE Select: NM_001927
dbSNP: rs150370918
Type: single nucleotide variant
Location: chr2:219420551 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73
Residue 264: the if rod domain; the 'linker 12' 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.Asp264Asn Uncertain significance ★ ⚠ 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-asp264 (accessed [today's date]).

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