Is DYM p.Pro670Ser (c.2008C>T) pathogenic?

DYM p.Pro670Ser (c.2008C>T) is classified Uncertain significance in DYM (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-03). AlphaMissense: ambiguous (0.3444); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DYM p.Pro670Ser (c.2008C>T)?

DYM p.Pro670Ser (c.2008C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DYM p.Pro670Ser (c.2008C>T) in the general population?

DYM p.Pro670Ser (c.2008C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DYM p.Pro670Ser (c.2008C>T)?

AlphaMissense predicts ambiguous (score 0.3444) — an in-silico prediction, not a clinical call.

DYM p.Pro670Ser

c.2008C>T · rs2513346305 · VCV2264214

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3444 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3444	ambiguous
REVEL	0.745	pathogenic-leaning
SaProt	LLR -5.71	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 12	GERP 2.6, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 75 kb · p 0.42 · regional, not allelic
Overall
CADD	27.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P615S vs ClinVar P670S) — verify the residue.

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.Pro670Ser
Coding: c.2008C>T
MANE Select: NM_001353214
dbSNP: rs2513346305
Type: single nucleotide variant
Location: chr18:49097419 (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.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
DYM p.Arg673Gly 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-pro670ser (accessed [today's date]).

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