Is DYM p.Arg70Ter (c.208C>T) pathogenic?

DYM p.Arg70Ter (c.208C>T) is classified Pathogenic/Likely pathogenic in DYM (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-09-17). Very rare (popmax 0.0028%, nfe); Associated with Dyggve-Melchior-Clausen disease.

What condition is associated with DYM p.Arg70Ter (c.208C>T)?

DYM p.Arg70Ter (c.208C>T) is associated with Dyggve-Melchior-Clausen disease (ClinVar).

How common is DYM p.Arg70Ter (c.208C>T) in the general population?

DYM p.Arg70Ter (c.208C>T) is very rare (popmax 0.0028%, nfe) (gnomAD).

How is Dyggve-Melchior-Clausen disease inherited?

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

DYM p.Arg70Ter

c.208C>T · rs768509996 · VCV449561

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0028%, nfe)

Conditions

Dyggve-Melchior-Clausen disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 18
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Overall
CADD	40.0	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 0.0028% European (non-Finnish) · 33/1,179,166 alleles

Filtering AF 0.002% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00176%

Overall 0.00217% 35/1,612,772 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0028%	35,732
East Asian	0.00223%	44,770
South Asian	0.0011%	91,048

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.Arg70Ter
Coding: c.208C>T
MANE Select: NM_001353214
dbSNP: rs768509996
Type: single nucleotide variant
Location: chr18:49379744 (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.Arg70Gln Uncertain significance ★ ⚠ same residue
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
DYM p.Gln306Ter Pathogenic/Likely pathogenic ★★ same condition
DYM p.Leu20Ter 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-arg70ter (accessed [today's date]).

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