Is DYM p.Ser542= (c.1626T>C) pathogenic?

DYM p.Ser542= (c.1626T>C) is classified Likely benign in DYM (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-20). Very rare (popmax 0.00112%, sas); Associated with Inborn genetic diseases.

What condition is associated with DYM p.Ser542= (c.1626T>C)?

DYM p.Ser542= (c.1626T>C) is associated with Inborn genetic diseases (ClinVar).

How common is DYM p.Ser542= (c.1626T>C) in the general population?

DYM p.Ser542= (c.1626T>C) is very rare (popmax 0.00112%, sas) (gnomAD).

DYM p.Ser542=

c.1626T>C · VCV3506003

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00112%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.7	GERP 1.5, phastCons 1
Overall
CADD	12.55	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00112% South Asian · 1/89,452 alleles

Overall 0.000125% 2/1,600,384 alleles · very rare exomes 2/1,448,038 · genomes 0/152,346 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00112%	89,452
European (non-Finnish)	8.54e-05%	1,171,001

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.Ser542=
Coding: c.1626T>C
MANE Select: NM_001353214
Type: single nucleotide variant
Location: chr18:49163787 (GRCh38)
Gene constraint: LOEUF 1.081 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 87.91
Residue 542: a UniProt-annotated variant site (in smc1)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DYM p.Tyr132Ter Pathogenic/Likely pathogenic ★★ same condition
DYM p.Ala254Ser Uncertain significance ★★ ⚠ same condition
DYM p.Ala270Val Uncertain significance ★★ ⚠ same condition
DYM p.Ala300Val Uncertain significance ★★ ⚠ same condition
DYM p.Ala327Asp Uncertain significance ★★ ⚠ same condition
DYM p.Ala668Val Uncertain significance ★★ ⚠ same condition
DYM p.Arg475His Uncertain significance ★★ ⚠ same condition
DYM p.Arg673Gly Uncertain significance ★★ ⚠ 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-ser542 (accessed [today's date]).

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