Is DYM p.Cys94Tyr (c.281G>A) pathogenic?

DYM p.Cys94Tyr (c.281G>A) is classified Uncertain significance in DYM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-04). AlphaMissense: likely pathogenic (0.6723); Ultra-rare (popmax 0.0334%, amr); Associated with Inborn genetic diseases.

What condition is associated with DYM p.Cys94Tyr (c.281G>A)?

DYM p.Cys94Tyr (c.281G>A) is associated with Inborn genetic diseases (ClinVar).

How common is DYM p.Cys94Tyr (c.281G>A) in the general population?

DYM p.Cys94Tyr (c.281G>A) is ultra-rare (popmax 0.0334%, amr) (gnomAD).

What do computational predictors say about DYM p.Cys94Tyr (c.281G>A)?

AlphaMissense predicts likely pathogenic (score 0.6723) — an in-silico prediction, not a clinical call.

DYM p.Cys94Tyr

c.281G>A · rs1049649508 · VCV1425943

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6723 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0334%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6723	likely pathogenic
REVEL	0.868	moderately pathogenic-leaning
SaProt	LLR -6.87	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.1, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 158 kb · p 0.51 · regional, not allelic
Overall
CADD	24.1	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 0.0334% Admixed American · 20/59,966 alleles

Filtering AF 0.0221% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0184%

Overall 0.00155% 25/1,610,372 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0334%	2,998
Remaining individualsnot grpmax-eligible	0.00802%	12,470

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.Cys94Tyr
Coding: c.281G>A
MANE Select: NM_001353214
dbSNP: rs1049649508
Type: single nucleotide variant
Location: chr18:49379671 (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

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

Similar variants

DYM p.Cys94Gly Uncertain significance ★ ⚠ same residue
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

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-cys94tyr (accessed [today's date]).

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