Is DYM p.His551fs (c.1650dup) pathogenic?

DYM p.His551fs (c.1650dup) is classified Pathogenic in DYM (ClinVar, Single submitter, 1 submitter; last evaluated 2020-10-01). Ultra-rare (gnomAD MAF 7.149e-07); Associated with Dyggve-Melchior-Clausen disease.

What condition is associated with DYM p.His551fs (c.1650dup)?

DYM p.His551fs (c.1650dup) is associated with Dyggve-Melchior-Clausen disease (ClinVar).

How common is DYM p.His551fs (c.1650dup) in the general population?

DYM p.His551fs (c.1650dup) is ultra-rare (gnomAD MAF 7.149e-07) (gnomAD).

How is Dyggve-Melchior-Clausen disease inherited?

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

DYM p.His551fs

c.1650dup · rs2087498329 · VCV1048086

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (gnomAD MAF 7.149e-07)

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 15 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.7, phastCons 1

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

Population frequency

dbSNP / gnomAD

Global frequency 7.15e-05% via dbSNP · ultra-rare

No ancestry breakdown or filtering allele frequency is available for this variant, so BA1/BS1 cannot be assessed from this figure alone.

Variant & gene context

Gene: DYM
Protein: p.His551fs
Coding: c.1650dup
MANE Select: NM_001353214
dbSNP: rs2087498329
Type: Duplication
Location: chr18:49163762 (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.Glu149fs Pathogenic ★ same condition
DYM p.Pro237fs Pathogenic ★ same condition
DYM p.Trp33fs Pathogenic same condition
DYM c.1728+2T>C Pathogenic/Likely pathogenic ★★ same condition
DYM c.947-2A>G Pathogenic/Likely pathogenic ★★ same condition
DYM p.Arg204Ter Pathogenic ★★ same condition
DYM p.Arg428Ter Pathogenic/Likely pathogenic ★★ same condition
DYM p.Arg588Ter 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-his551fs (accessed [today's date]).

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