Is DYM p.Leu20Ter (c.59T>A) pathogenic?

DYM p.Leu20Ter (c.59T>A) is classified Pathogenic in DYM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-05-22). Absent from gnomAD v4.1; Associated with Dyggve-Melchior-Clausen disease.

What condition is associated with DYM p.Leu20Ter (c.59T>A)?

DYM p.Leu20Ter (c.59T>A) is associated with Dyggve-Melchior-Clausen disease (ClinVar).

How common is DYM p.Leu20Ter (c.59T>A) in the general population?

DYM p.Leu20Ter (c.59T>A) is absent from gnomAD v4.1 (gnomAD).

How is Dyggve-Melchior-Clausen disease inherited?

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

DYM p.Leu20Ter

c.59T>A · rs2074694091 · VCV1322791

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 2 of 18
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Overall
CADD	37.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DYM
Protein: p.Leu20Ter
Coding: c.59T>A
MANE Select: NM_001353214
dbSNP: rs2074694091
Type: single nucleotide variant
Location: chr18:49430336 (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.Leu20Phe 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.Arg70Ter Pathogenic/Likely pathogenic ★★ same condition
DYM p.Gln306Ter 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-leu20ter (accessed [today's date]).

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