Is DMPK p.Pro257= (c.771C>T) pathogenic?

DMPK p.Pro257= (c.771C>T) is classified Likely benign in DMPK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-14). Ultra-rare (popmax 0.0245%, eas); Associated with Inborn genetic diseases.

What condition is associated with DMPK p.Pro257= (c.771C>T)?

DMPK p.Pro257= (c.771C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DMPK p.Pro257= (c.771C>T) in the general population?

DMPK p.Pro257= (c.771C>T) is ultra-rare (popmax 0.0245%, eas) (gnomAD).

DMPK p.Pro257=

c.771C>T · VCV3911413

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0245%, eas)

Conditions

Inborn genetic diseases

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 -6.6	GERP -4.3
Overall
CADD	3.372	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0245% East Asian · 11/44,888 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.00341% 55/1,612,918 alleles · ultra-rare exomes 49/1,460,726 · genomes 6/152,192 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0245%	4,081
Middle Eastern	0.0164%	6,084
European (non-Finnish)	0.00339%	29,501
Remaining individualsnot grpmax-eligible	0.0032%	31,235
South Asian	0.0011%	91,088

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.Pro257=
Coding: c.771C>T
MANE Select: NM_004409
Type: single nucleotide variant
Location: chr19:45777778 (GRCh38)
Gene constraint: LOEUF 0.67 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.91 · 2 PDB
Residue 257: the protein kinase domain

Full DMPK 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

DMPK c.161-106C>A Uncertain significance ★ same condition
DMPK c.161-115A>G Uncertain significance ★ same condition
DMPK c.161-123A>C Uncertain significance ★ same condition
DMPK c.161-146G>A Uncertain significance ★ same condition
DMPK c.161-27G>T Uncertain significance ★ same condition
DMPK c.161-48G>C Uncertain significance ★ same condition
DMPK c.161-6C>T Uncertain significance ★ same condition
DMPK c.161-99G>T 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/dmpk-p-pro257 (accessed [today's date]).

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