Is DYM p.Arg204Ter (c.610C>T) pathogenic?

DYM p.Arg204Ter (c.610C>T) is classified Pathogenic in DYM (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-03-17). Very rare (popmax 0.00223%, eas); Associated with Dyggve-Melchior-Clausen disease.

What condition is associated with DYM p.Arg204Ter (c.610C>T)?

DYM p.Arg204Ter (c.610C>T) is associated with Dyggve-Melchior-Clausen disease (ClinVar).

How common is DYM p.Arg204Ter (c.610C>T) in the general population?

DYM p.Arg204Ter (c.610C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

How is Dyggve-Melchior-Clausen disease inherited?

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

DYM p.Arg204Ter

c.610C>T · rs752868357 · VCV2503430

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

Dyggve-Melchior-Clausen disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 18
Splicing
SpliceAI	Δ0.40	donor gain · deltas
Constraint at this position
Conservation	phyloP 8.5	GERP 2.2, phastCons 1
Overall
CADD	48.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,844 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.00116% 17/1,461,388 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,844
South Asian	0.0022%	45,536
Admixed American	0.00167%	60,016
European (non-Finnish)	0.0011%	90,747

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: DYM
Protein: p.Arg204Ter
Coding: c.610C>T
MANE Select: NM_001353214
dbSNP: rs752868357
Type: single nucleotide variant
Location: chr18:49333738 (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 c.1728+2T>C Pathogenic/Likely pathogenic ★★ same condition
DYM c.947-2A>G Pathogenic/Likely pathogenic ★★ same condition
DYM p.Arg428Ter Pathogenic/Likely pathogenic ★★ same condition
DYM p.Arg588Ter Pathogenic ★★ same condition
DYM p.Arg70Ter Pathogenic/Likely pathogenic ★★ same condition
DYM p.Gln306Ter Pathogenic/Likely pathogenic ★★ same condition
DYM p.Leu20Ter Pathogenic ★★ same condition
DYM p.Tyr132Ter 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-arg204ter (accessed [today's date]).

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