Is DES p.Ala273fs (c.816dup) pathogenic?

DES p.Ala273fs (c.816dup) is classified Likely pathogenic in DES (ClinVar, No assertion criteria, 3 submitters). Absent from gnomAD.

How common is DES p.Ala273fs (c.816dup) in the general population?

DES p.Ala273fs (c.816dup) is absent from gnomAD (gnomAD).

DES p.Ala273fs

c.816dup · rs2125167896 · VCV1328046

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DES
Protein: p.Ala273fs
Coding: c.816dup
MANE Select: NM_001927
dbSNP: rs2125167896
Type: Duplication
Location: chr2:219420573 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73
Residue 273: the if rod domain; the 'interaction with neb' region; the 'coil 2a' region

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

Similar variants

DES p.Ala273Pro Uncertain significance ★★ ⚠ same residue
DES p.Ala273Ser Uncertain significance ★★ ⚠ same residue
DES p.Ala273Thr Uncertain significance ★★ ⚠ same residue
DES p.Leu66fs Pathogenic/Likely pathogenic ★★ same type
DES c.1023+6_1023+24dup Uncertain significance ★★ same type
DES c.1371+2dup Uncertain significance ★★ same type
DES c.-30_-18dup Benign ★★ same type
DES p.Asp343_Ser344dup Likely pathogenic ★ same type

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-ala273fs (accessed [today's date]).

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