Is DYM p.Gln306Ter (c.916C>T) pathogenic?

DYM p.Gln306Ter (c.916C>T) is classified Pathogenic/Likely pathogenic in DYM (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-08-06). Absent from gnomAD v4.1; Associated with Dyggve-Melchior-Clausen disease.

What condition is associated with DYM p.Gln306Ter (c.916C>T)?

DYM p.Gln306Ter (c.916C>T) is associated with Dyggve-Melchior-Clausen disease, early-onset non-syndromic cataract (ClinVar).

How common is DYM p.Gln306Ter (c.916C>T) in the general population?

DYM p.Gln306Ter (c.916C>T) 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.Gln306Ter

c.916C>T · rs201540129 · VCV2574672

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 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 9 of 18
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, 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

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.Gln306Ter
Coding: c.916C>T
MANE Select: NM_001353214
dbSNP: rs201540129
Type: single nucleotide variant
Location: chr18:49286464 (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

Also linked: early-onset non-syndromic cataract

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.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.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-gln306ter (accessed [today's date]).

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