Is DYM p.Val638= (c.1914G>C) pathogenic?

DYM p.Val638= (c.1914G>C) is classified Benign/Likely benign in DYM (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-01). Common (popmax 12.5%, afr) — too common for a highly-penetrant pathogenic allele; Associated with connective tissue disorder.

What condition is associated with DYM p.Val638= (c.1914G>C)?

DYM p.Val638= (c.1914G>C) is associated with connective tissue disorder (ClinVar).

DYM p.Val638=

Q: How common is DYM p.Val638= (c.1914G>C) in the general population?

DYM p.Val638= (c.1914G>C) is common (popmax 12.5%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1914G>C · rs60818038 · VCV326893

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 12.5%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

connective tissue disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.83	GERP -2, phastCons 1
Overall
CADD	11.74	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 12.5% African / African-American · 9,402/74,974 alleles

Filtering AF 12.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 12.2%

Overall 0.661% 10,657/1,613,348 alleles · common exomes 5,244/1,461,078 · genomes 5,413/152,270 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	12.5%	8
Remaining individualsnot grpmax-eligible	0.826%	121
Admixed American	0.784%	128
Middle Eastern	0.231%	432
European (non-Finnish)	0.0202%	4,956
South Asian	0.0165%	6,070
Finnishnot grpmax-eligible	0.00313%	31,989

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.Val638=
Coding: c.1914G>C
MANE Select: NM_001353214
dbSNP: rs60818038
Type: single nucleotide variant
Location: chr18:49097513 (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.Val638Ala Uncertain significance ★ ⚠ same residue
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 c.620+4T>G Conflicting classifications of pathogenicity ★ same condition
DYM p.Val181= 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-val638 (accessed [today's date]).

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