Is DYM p.Glu87Lys (c.259G>A) pathogenic?

DYM p.Glu87Lys (c.259G>A) is classified Pathogenic in DYM (ClinVar, Multiple submitters, 4 submitters; last evaluated 2022-09-01). AlphaMissense: likely pathogenic (0.9681); Very rare (popmax 0.00167%, amr); Associated with DYM-related disorder.

What condition is associated with DYM p.Glu87Lys (c.259G>A)?

DYM p.Glu87Lys (c.259G>A) is associated with DYM-related disorder, Smith-McCort dysplasia 1 (ClinVar).

How common is DYM p.Glu87Lys (c.259G>A) in the general population?

DYM p.Glu87Lys (c.259G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about DYM p.Glu87Lys (c.259G>A)?

AlphaMissense predicts likely pathogenic (score 0.9681) — an in-silico prediction, not a clinical call.

DYM p.Glu87Lys

c.259G>A · rs120074164 · VCV3189

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9681 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DYM-related disorder

Computational evidence

Protein change
AlphaMissense	0.9681	likely pathogenic ✓ concordant with ClinVar
REVEL	0.873	moderately pathogenic-leaning
SaProt	LLR -8.37	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.1, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 158 kb · p 0.51 · 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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,992 alleles

Overall 0.000137% 2/1,460,946 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,992
European (non-Finnish)	8.48e-05%	1,179,400

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.Glu87Lys
Coding: c.259G>A
MANE Select: NM_001353214
dbSNP: rs120074164
Type: single nucleotide variant
Location: chr18:49379693 (GRCh38)
Gene constraint: LOEUF 1.081 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 87.91
Residue 87: a UniProt-annotated variant site (in smc1; does not affect protein localization)

Full DYM gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DYM-related disorder

Also linked: Smith-McCort dysplasia 1

Similar variants

DYM c.947-2A>G Pathogenic/Likely pathogenic ★★ same condition
DYM p.Arg588Ter Pathogenic ★★ same condition
DYM p.Tyr132Ter Pathogenic/Likely pathogenic ★★ same condition
DYM p.Arg369His Uncertain significance ★★ ⚠ same condition
DYM c.193+9G>A Benign ★★ same condition
DYM c.621-2A>G Pathogenic ★ same condition
DYM p.Arg455Ter Pathogenic ★ same condition
DYM p.Leu36Arg 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-glu87lys (accessed [today's date]).

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