Is DYM p.Asp408fs (c.1222del) pathogenic?

DYM p.Asp408fs (c.1222del) is classified Pathogenic in DYM (ClinVar, No assertion criteria, 1 submitter). Absent from gnomAD; Associated with Dyggve-Melchior-Clausen disease.

What condition is associated with DYM p.Asp408fs (c.1222del)?

DYM p.Asp408fs (c.1222del) is associated with Dyggve-Melchior-Clausen disease (ClinVar).

How common is DYM p.Asp408fs (c.1222del) in the general population?

DYM p.Asp408fs (c.1222del) is absent from gnomAD (gnomAD).

How is Dyggve-Melchior-Clausen disease inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

DYM p.Asp408fs

c.1222del · rs2145537667 · VCV981237

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Dyggve-Melchior-Clausen disease

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 11 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 2, 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: DYM
Protein: p.Asp408fs
Coding: c.1222del
MANE Select: NM_001353214
dbSNP: rs2145537667
Type: Deletion
Location: chr18:49272207 (GRCh38)
Gene constraint: LOEUF 1.081 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 87.91

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

Disease context

Dyggve-Melchior-Clausen disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Dyggve-Melchior-Clausen disease (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

DYM p.Lys681fs Pathogenic/Likely pathogenic ★★ same condition
DYM p.Pro279fs Pathogenic ★ same condition
DYM p.Ser322fs Pathogenic ★ same condition
DYM c.1626-14_1626-4del Uncertain significance ★ same condition
DYM p.His393fs Pathogenic same condition
DYM p.Thr255fs Pathogenic same condition
DYM c.1728+2T>C Pathogenic/Likely pathogenic ★★ same condition
DYM c.947-2A>G Pathogenic/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/dym-p-asp408fs (accessed [today's date]).

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