Is DMPK p.Pro337Arg (c.1010C>G) pathogenic?

DMPK p.Pro337Arg (c.1010C>G) is classified Likely benign in DMPK (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-02-05). AlphaMissense: likely benign (0.1078); Rare (popmax 0.808%, mid); Associated with DMPK-related disorder.

What condition is associated with DMPK p.Pro337Arg (c.1010C>G)?

DMPK p.Pro337Arg (c.1010C>G) is associated with DMPK-related disorder (ClinVar).

How common is DMPK p.Pro337Arg (c.1010C>G) in the general population?

DMPK p.Pro337Arg (c.1010C>G) is rare (popmax 0.808%, mid) (gnomAD).

What do computational predictors say about DMPK p.Pro337Arg (c.1010C>G)?

AlphaMissense predicts likely benign (score 0.1078) — an in-silico prediction, not a clinical call.

DMPK p.Pro337Arg

c.1010C>G · rs142936719 · VCV3053136

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1078 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.808%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

DMPK-related disorder

Computational evidence

Protein change
AlphaMissense	0.1078	likely benign
REVEL	0.449	indeterminate
SaProt	LLR -10.72	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 7,198 bp · p 0.0012 · regional, not allelic
Overall
CADD	26.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.808% Middle Eastern · 49/6,062 alleles

Filtering AF 0.628% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.564%

Overall 0.0811% 1,309/1,613,478 alleles · rare exomes 1,217/1,461,122 · genomes 92/152,356 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.808%	124
South Asian	0.415%	241
Remaining individualsnot grpmax-eligible	0.131%	762
Admixed American	0.09%	1,111
European (non-Finnish)	0.0614%	1,630
Ashkenazi Jewishnot grpmax-eligible	0.0169%	5,921
African / African-American	0.0147%	6,823
Finnishnot grpmax-eligible	0.0079%	12,662
East Asian	0.00223%	44,888

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.Pro337Arg
Coding: c.1010C>G
MANE Select: NM_004409
dbSNP: rs142936719
Type: single nucleotide variant
Location: chr19:45777463 (GRCh38)
Gene constraint: LOEUF 0.67 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.91 · 2 PDB
Residue 337: the protein kinase domain; an α-helix

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

Disease context

DMPK-related disorder

Similar variants

DMPK c.161-5C>G Likely benign same condition
DMPK p.Ala425= Likely benign same condition
DMPK p.Ala435= Likely benign same condition
DMPK p.Asp69Asn Benign same condition
DMPK p.Gly326= Likely benign same condition
DMPK p.His296= Likely benign same condition
DMPK p.Lys89= Likely benign same condition
DMPK p.Thr225= Likely benign 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-pro337arg (accessed [today's date]).

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