Is DYM p.Val180Gly (c.539T>G) pathogenic?

DYM p.Val180Gly (c.539T>G) is classified Uncertain significance in DYM (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-22). AlphaMissense: ambiguous (0.3642); Absent from gnomAD v4.1.

How common is DYM p.Val180Gly (c.539T>G) in the general population?

DYM p.Val180Gly (c.539T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DYM p.Val180Gly (c.539T>G)?

AlphaMissense predicts ambiguous (score 0.3642) — an in-silico prediction, not a clinical call.

DYM p.Val180Gly

c.539T>G · rs2146865937 · VCV1438264

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3642 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3642	ambiguous
REVEL	0.751	pathogenic-leaning
SaProt	LLR -8.59	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.3, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 158 kb · p 0.51 · regional, not allelic
Overall
CADD	24.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DYM
Protein: p.Val180Gly
Coding: c.539T>G
MANE Select: NM_001353214
dbSNP: rs2146865937
Type: single nucleotide variant
Location: chr18:49333809 (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

Similar variants

DYM c.1728+2T>C Pathogenic/Likely pathogenic ★★ same type
DYM c.947-2A>G Pathogenic/Likely pathogenic ★★ same type
DYM p.Arg204Ter Pathogenic ★★ same type
DYM p.Arg428Ter Pathogenic/Likely pathogenic ★★ same type
DYM p.Arg588Ter Pathogenic ★★ same type
DYM p.Arg70Ter Pathogenic/Likely pathogenic ★★ same type
DYM p.Gln306Ter Pathogenic/Likely pathogenic ★★ same type
DYM p.Glu87Lys 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-val180gly (accessed [today's date]).

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