Is DMPK p.Pro352Ser (c.1054C>T) pathogenic?

DMPK p.Pro352Ser (c.1054C>T) is classified Uncertain significance in DMPK (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-28). AlphaMissense: likely pathogenic (0.6332); Absent from gnomAD v4.1.

How common is DMPK p.Pro352Ser (c.1054C>T) in the general population?

DMPK p.Pro352Ser (c.1054C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DMPK p.Pro352Ser (c.1054C>T)?

AlphaMissense predicts likely pathogenic (score 0.6332) — an in-silico prediction, not a clinical call.

DMPK p.Pro352Ser

c.1054C>T · VCV4689183

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6332 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6332	likely pathogenic
REVEL	0.201	benign-leaning
SaProt	LLR -10.48	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP -0.34, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 7,198 bp · p 0.0012 · regional, not allelic
Overall
CADD	25.4	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: DMPK
Protein: p.Pro352Ser
Coding: c.1054C>T
MANE Select: NM_004409
Type: single nucleotide variant
Location: chr19:45777419 (GRCh38)
Gene constraint: LOEUF 0.67 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.91 · 2 PDB
Residue 352: the agc-kinase c-terminal domain

Full DMPK gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DMPK p.Pro352= Likely benign ★ same residue
DMPK p.Arg210Cys Uncertain significance ★★ ⚠ same type
DMPK c.161-459C>T Likely benign ★★ same type
DMPK c.581+6T>C Benign ★★ same type
DMPK c.882+8C>T Likely benign ★★ same type
DMPK p.Leu423Val Benign ★★ same type
DMPK p.Pro257= Likely benign ★★ same type
DMPK c.161-106C>A Uncertain significance ★ 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/dmpk-p-pro352ser (accessed [today's date]).

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