Is DMPK p.Pro168= (c.504G>A) pathogenic?

DMPK p.Pro168= (c.504G>A) is classified Benign in DMPK (ClinVar, Single submitter, 2 submitters). Common (popmax 10.8%, afr) — too common for a highly-penetrant pathogenic allele.

DMPK p.Pro168=

Q: How common is DMPK p.Pro168= (c.504G>A) in the general population?

DMPK p.Pro168= (c.504G>A) is common (popmax 10.8%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.504G>A · rs34510782 · VCV128901

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 10.8%, afr) — too common for a highly-penetrant pathogenic allele

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 -5.4	GERP -4.3
Overall
CADD	2.766	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 10.8% African / African-American · 8,109/75,022 alleles

Filtering AF 10.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 10.5%

Overall 0.596% 9,617/1,613,950 alleles · common exomes 4,995/1,461,666 · genomes 4,622/152,284 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	10.8%	9
Remaining individualsnot grpmax-eligible	0.835%	120
Admixed American	0.73%	137
Middle Eastern	0.693%	144
East Asian	0.0513%	1,951
European (non-Finnish)	0.0392%	2,554
South Asian	0.0231%	4,338

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.Pro168=
Coding: c.504G>A
MANE Select: NM_004409
dbSNP: rs34510782
Type: single nucleotide variant
Location: chr19:45778570 (GRCh38)
Gene constraint: LOEUF 0.67 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.91 · 2 PDB
Residue 168: the protein kinase domain; an α-helix

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-pro168 (accessed [today's date]).

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