Is DMPK p.Ser228= (c.684G>C) pathogenic?

DMPK p.Ser228= (c.684G>C) is classified Likely benign in DMPK (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-18). Very rare (popmax 0.000848%, nfe).

How common is DMPK p.Ser228= (c.684G>C) in the general population?

DMPK p.Ser228= (c.684G>C) is very rare (popmax 0.000848%, nfe) (gnomAD).

DMPK p.Ser228=

c.684G>C · VCV4942930

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000848%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.5	GERP -4.3
Overall
CADD	0.397	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000848% European (non-Finnish) · 10/1,179,284 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000622% 10/1,607,900 alleles · very rare exomes 10/1,455,534 · genomes 0/152,366 · joint denominator

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: DMPK
Protein: p.Ser228=
Coding: c.684G>C
MANE Select: NM_004409
Type: single nucleotide variant
Location: chr19:45777865 (GRCh38)
Gene constraint: LOEUF 0.67 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.91 · 2 PDB
Residue 228: a modified residue (phosphoserine; by autocatalysis); the protein kinase domain

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

Similar variants

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
DMPK c.161-115A>G 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-ser228 (accessed [today's date]).

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