Is DYM p.Val181= (c.543T>G) pathogenic?

DYM p.Val181= (c.543T>G) is classified Conflicting classifications of pathogenicity in DYM (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-11-19). Ultra-rare (popmax 0.056%, sas); Associated with connective tissue disorder.

What condition is associated with DYM p.Val181= (c.543T>G)?

DYM p.Val181= (c.543T>G) is associated with connective tissue disorder (ClinVar).

How common is DYM p.Val181= (c.543T>G) in the general population?

DYM p.Val181= (c.543T>G) is ultra-rare (popmax 0.056%, sas) (gnomAD).

DYM p.Val181=

c.543T>G · rs759683937 · VCV1702398

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.056%, sas)

Conditions

connective tissue disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.4	GERP -3, phastCons 1
Overall
CADD	6.773	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.056% South Asian · 51/91,082 alleles

Filtering AF 0.0437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0394%

Overall 0.00328% 53/1,613,486 alleles · ultra-rare exomes 49/1,461,236 · genomes 4/152,250 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.056%	1,786
Remaining individualsnot grpmax-eligible	0.0032%	31,238

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.Val181=
Coding: c.543T>G
MANE Select: NM_001353214
dbSNP: rs759683937
Type: single nucleotide variant
Location: chr18:49333805 (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

connective tissue disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DYM p.Asp724Asn Uncertain significance ★★ ⚠ same condition
DYM c.193+9G>A Benign ★★ same condition
DYM p.Leu107= Benign/Likely benign ★★ same condition
DYM p.Leu114= Benign/Likely benign ★★ same condition
DYM p.Ser141Gly Benign/Likely benign ★★ same condition
DYM p.Val638= Benign/Likely benign ★★ same condition
DYM c.620+4T>G Conflicting classifications of pathogenicity ★ same condition
DYM c.1728+2T>C Pathogenic/Likely pathogenic ★★ same type

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-val181 (accessed [today's date]).

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