Is DYM p.Leu107= (c.321G>A) pathogenic?

DYM p.Leu107= (c.321G>A) is classified Benign/Likely benign in DYM (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-04). Low-frequency (popmax 1.48%, eas); Associated with connective tissue disorder.

What condition is associated with DYM p.Leu107= (c.321G>A)?

DYM p.Leu107= (c.321G>A) is associated with connective tissue disorder (ClinVar).

How common is DYM p.Leu107= (c.321G>A) in the general population?

DYM p.Leu107= (c.321G>A) is low-frequency (popmax 1.48%, eas) (gnomAD).

DYM p.Leu107=

c.321G>A · rs16950519 · VCV326905

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.48%, eas)

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 2.7	GERP -0.89, phastCons 1
Overall
CADD	11.74	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.48% East Asian · 661/44,728 alleles

Filtering AF 1.38% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.35%

Overall 0.0483% 779/1,613,278 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	1.48%	68
Remaining individualsnot grpmax-eligible	0.0576%	1,735
South Asian	0.0527%	1,897
Admixed American	0.0167%	5,996
African / African-American	0.00267%	37,499
European (non-Finnish)	0.00187%	53,616

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.Leu107=
Coding: c.321G>A
MANE Select: NM_001353214
dbSNP: rs16950519
Type: single nucleotide variant
Location: chr18:49378667 (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.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 p.Val181= 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-leu107 (accessed [today's date]).

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