Is DMPK p.Ala613Ser (c.1837G>T) pathogenic?

DMPK p.Ala613Ser (c.1837G>T) is classified Likely benign in DMPK (ClinVar, Single submitter, 1 submitter; last evaluated 2020-05-03). AlphaMissense: likely benign (0.0868); Ultra-rare (popmax 0.0668%, mid); Associated with myotonic dystrophy type 1.

What condition is associated with DMPK p.Ala613Ser (c.1837G>T)?

DMPK p.Ala613Ser (c.1837G>T) is associated with myotonic dystrophy type 1 (ClinVar).

How common is DMPK p.Ala613Ser (c.1837G>T) in the general population?

DMPK p.Ala613Ser (c.1837G>T) is ultra-rare (popmax 0.0668%, mid) (gnomAD).

How is Steinert myotonic dystrophy inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about DMPK p.Ala613Ser (c.1837G>T)?

AlphaMissense predicts likely benign (score 0.0868) — an in-silico prediction, not a clinical call.

DMPK p.Ala613Ser

c.1837G>T · rs1003871860 · VCV523044

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0868 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0668%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

myotonic dystrophy type 1

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.0868	likely benign
REVEL	0.058	moderately benign-leaning
SaProt	LLR -6.41	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.59	GERP -0.93
Regional constraint	o/e 1.15	unconstrained · MANE · 7,198 bp · p 0.0012 · regional, not allelic
Overall
CADD	13.19	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 0.0668% Middle Eastern · 4/5,990 alleles

Filtering AF 0.0227% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00271% 42/1,550,822 alleles · ultra-rare exomes 38/1,398,454 · genomes 4/152,368 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0668%	1,497
Remaining individualsnot grpmax-eligible	0.00499%	20,033
European (non-Finnish)	0.00279%	35,841
African / African-American	0.00273%	36,587
Admixed American	0.00196%	51,026

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.Ala613Ser
Coding: c.1837G>T
MANE Select: NM_004409
dbSNP: rs1003871860
Type: single nucleotide variant
Location: chr19:45770541 (GRCh38)

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

Disease context

myotonic dystrophy type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Steinert myotonic dystrophy (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Antenatal, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Europe)

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-ala613ser (accessed [today's date]).

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