Is DMPK p.Val152= (c.456G>A) pathogenic?

DMPK p.Val152= (c.456G>A) is classified Benign in DMPK (ClinVar, Single submitter, 2 submitters). Common (popmax 9.32%, afr) — too common for a highly-penetrant pathogenic allele.

DMPK p.Val152=

Q: How common is DMPK p.Val152= (c.456G>A) in the general population?

DMPK p.Val152= (c.456G>A) is common (popmax 9.32%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.456G>A · rs34798952 · VCV128900

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 9.32%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.33	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 2.7	GERP -0.34, phastCons 1
Overall
CADD	16.88	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.32% African / African-American · 6,991/75,014 alleles

Filtering AF 9.14% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.06%

Overall 0.505% 8,149/1,613,854 alleles · common exomes 4,132/1,461,562 · genomes 4,017/152,292 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	9.32%	11
Remaining individualsnot grpmax-eligible	0.701%	143
Admixed American	0.623%	160
Middle Eastern	0.165%	606
European (non-Finnish)	0.0273%	3,665
South Asian	0.0154%	6,506

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.Val152=
Coding: c.456G>A
MANE Select: NM_004409
dbSNP: rs34798952
Type: single nucleotide variant
Location: chr19:45778618 (GRCh38)
Gene constraint: LOEUF 0.67 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.91 · 2 PDB
Residue 152: the protein kinase domain

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

Similar variants

DMPK p.Val152Met 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-val152 (accessed [today's date]).

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