Is DMPK p.Ala464= (c.1392C>A) pathogenic?

DMPK p.Ala464= (c.1392C>A) is classified Likely benign in DMPK (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-02-20). Rare (popmax 0.116%, mid); Associated with DMPK-related disorder.

What condition is associated with DMPK p.Ala464= (c.1392C>A)?

DMPK p.Ala464= (c.1392C>A) is associated with DMPK-related disorder (ClinVar).

How common is DMPK p.Ala464= (c.1392C>A) in the general population?

DMPK p.Ala464= (c.1392C>A) is rare (popmax 0.116%, mid) (gnomAD).

DMPK p.Ala464=

c.1392C>A · rs147014815 · VCV3041374

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.116%, mid)

Conditions

DMPK-related disorder

⚠ 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
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -9.2	GERP -3.3
Overall
CADD	0.118	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.116% Middle Eastern · 7/6,036 alleles

Filtering AF 0.0544% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0385%

Overall 0.0205% 326/1,593,752 alleles · rare exomes 311/1,441,470 · genomes 15/152,282 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.154%	648
Middle Easterngrpmax	0.116%	862
Remaining individualsnot grpmax-eligible	0.0357%	2,802
European (non-Finnish)	0.0214%	4,681
Admixed American	0.00173%	57,638
African / African-American	0.00134%	74,554

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala464=
Coding: c.1392C>A
MANE Select: NM_004409
dbSNP: rs147014815
Type: single nucleotide variant
Location: chr19:45771881 (GRCh38)

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

Disease context

DMPK-related disorder

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-ala464 (accessed [today's date]).

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