Is DYM p.Ser141Gly (c.421A>G) pathogenic?

DYM p.Ser141Gly (c.421A>G) is classified Benign/Likely benign in DYM (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-26). AlphaMissense: likely benign (0.0541); Low-frequency (popmax 3.96%, afr); Associated with connective tissue disorder.

What condition is associated with DYM p.Ser141Gly (c.421A>G)?

DYM p.Ser141Gly (c.421A>G) is associated with connective tissue disorder (ClinVar).

How common is DYM p.Ser141Gly (c.421A>G) in the general population?

DYM p.Ser141Gly (c.421A>G) is low-frequency (popmax 3.96%, afr) (gnomAD).

What do computational predictors say about DYM p.Ser141Gly (c.421A>G)?

AlphaMissense predicts likely benign (score 0.0541) — an in-silico prediction, not a clinical call.

DYM p.Ser141Gly

c.421A>G · rs61729806 · VCV326903

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0541 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.96%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

connective tissue disorder

Computational evidence

Protein change
AlphaMissense	0.0541	likely benign
REVEL	0.208	benign-leaning
SaProt	LLR -7.60	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.046	GERP -1.6, phastCons 0.008
Regional constraint	o/e 1.03	unconstrained · MANE · 158 kb · p 0.51 · regional, not allelic
Overall
CADD	11.44	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 3.96% African / African-American · 2,962/74,840 alleles

Filtering AF 3.84% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.79%

Overall 0.228% 3,662/1,608,516 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.96%	25
South Asian	0.379%	264
Remaining individualsnot grpmax-eligible	0.3%	333
Admixed American	0.195%	513
Middle Eastern	0.116%	861
East Asian	0.00671%	14,901
European (non-Finnish)	0.00349%	28,665

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.Ser141Gly
Coding: c.421A>G
MANE Select: NM_001353214
dbSNP: rs61729806
Type: single nucleotide variant
Location: chr18:49378567 (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.Ser141Asn Likely pathogenic ★ ⚠ 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.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

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-ser141gly (accessed [today's date]).

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