Is DMPK p.Pro352= (c.1056C>T) pathogenic?

DMPK p.Pro352= (c.1056C>T) is classified Likely benign in DMPK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-16). Low-frequency (popmax 1.17%, afr).

How common is DMPK p.Pro352= (c.1056C>T) in the general population?

DMPK p.Pro352= (c.1056C>T) is low-frequency (popmax 1.17%, afr) (gnomAD).

DMPK p.Pro352=

c.1056C>T · VCV4942929

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 1.17%, afr)

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 1.1	GERP -4.2, phastCons 1
Overall
CADD	7.427	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.17% African / African-American · 879/75,038 alleles

Filtering AF 1.11% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.08%

Overall 0.0621% 1,002/1,613,386 alleles · low-frequency exomes 466/1,461,064 · genomes 536/152,322 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.17%	85
Admixed American	0.0867%	1,154
Remaining individualsnot grpmax-eligible	0.0752%	1,330
Middle Eastern	0.0495%	2,021
European (non-Finnish)	0.00178%	56,188

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.Pro352=
Coding: c.1056C>T
MANE Select: NM_004409
Type: single nucleotide variant
Location: chr19:45777417 (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.Pro352Ser Uncertain significance ★ ⚠ 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-pro352 (accessed [today's date]).

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