Is DYM p.Arg455Ter (c.1363C>T) pathogenic?

DYM p.Arg455Ter (c.1363C>T) is classified Pathogenic in DYM (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-20). Very rare (popmax 0.00269%, afr); Associated with DYM-related disorder.

What condition is associated with DYM p.Arg455Ter (c.1363C>T)?

DYM p.Arg455Ter (c.1363C>T) is associated with DYM-related disorder (ClinVar).

How common is DYM p.Arg455Ter (c.1363C>T) in the general population?

DYM p.Arg455Ter (c.1363C>T) is very rare (popmax 0.00269%, afr) (gnomAD).

DYM p.Arg455Ter

c.1363C>T · VCV4939028

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00269%, afr)

Conditions

DYM-related disorder

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 12 of 18
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP -0.39, 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

Grpmax group 0.00269% African / African-American · 2/74,350 alleles

Filtering AF 0.000446% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000167%

Overall 0.000252% 4/1,585,580 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00269%	37,175
European (non-Finnish)	0.000173%	577,117

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.Arg455Ter
Coding: c.1363C>T
MANE Select: NM_001353214
Type: single nucleotide variant
Location: chr18:49258382 (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

DYM-related disorder

Similar variants

DYM c.947-2A>G Pathogenic/Likely pathogenic ★★ same condition
DYM p.Arg588Ter Pathogenic ★★ same condition
DYM p.Glu87Lys Pathogenic ★★ same condition
DYM p.Arg369His Uncertain significance ★★ ⚠ same condition
DYM p.Ala307Val Uncertain significance ⚠ same condition
DYM p.Asn14Lys Uncertain significance ⚠ same condition
DYM p.Leu674Pro Uncertain significance ⚠ same condition
DYM p.Leu674= Likely benign 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-arg455ter (accessed [today's date]).

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