Is DYM p.Cys597Arg (c.1789T>C) pathogenic?

DYM p.Cys597Arg (c.1789T>C) is classified Pathogenic in DYM (ClinVar, No assertion criteria, 1 submitter; last evaluated 2009-01-01). AlphaMissense: likely pathogenic (0.997); Absent from gnomAD v4.1; Associated with Smith-McCort dysplasia 1.

What condition is associated with DYM p.Cys597Arg (c.1789T>C)?

DYM p.Cys597Arg (c.1789T>C) is associated with Smith-McCort dysplasia 1 (ClinVar).

How common is DYM p.Cys597Arg (c.1789T>C) in the general population?

DYM p.Cys597Arg (c.1789T>C) is absent from gnomAD v4.1 (gnomAD).

How is Smith-McCort dysplasia inherited?

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

What do computational predictors say about DYM p.Cys597Arg (c.1789T>C)?

AlphaMissense predicts likely pathogenic (score 0.997) — an in-silico prediction, not a clinical call.

DYM p.Cys597Arg

c.1789T>C · rs120074165 · VCV3193

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.997 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Smith-McCort dysplasia 1

Computational evidence

Protein change
AlphaMissense	0.997	likely pathogenic ✓ concordant with ClinVar · top 4% in DYM
REVEL	0.927	moderately pathogenic-leaning
SaProt	LLR -13.52	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 154 kb · p 7.5e-06 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM C542R vs ClinVar C597R) — verify the residue.

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.Cys597Arg
Coding: c.1789T>C
MANE Select: NM_001353214
dbSNP: rs120074165
Type: single nucleotide variant
Location: chr18:49118866 (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

Smith-McCort dysplasia 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Smith-McCort dysplasia (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

DYM p.Glu87Lys Pathogenic ★★ same condition
DYM p.Tyr132Ter Pathogenic/Likely pathogenic ★★ same condition
DYM c.193+9G>A Benign ★★ same condition
DYM c.621-2A>G Pathogenic ★ same condition
DYM p.Leu36Arg Likely pathogenic ★ same condition
DYM c.1251+12T>C Conflicting classifications of pathogenicity ★ same condition
DYM c.1461-8T>G Conflicting classifications of pathogenicity ★ same condition
DYM c.288-10G>A Conflicting classifications of pathogenicity ★ 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-cys597arg (accessed [today's date]).

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