Is DMPK p.Ala172Val (c.515C>T) pathogenic?

DMPK p.Ala172Val (c.515C>T) is classified Uncertain significance in DMPK (ClinVar, Single submitter, 2 submitters; last evaluated 2023-10-10). AlphaMissense: ambiguous (0.5135); Ultra-rare (popmax 0.0201%, eas); Associated with Inborn genetic diseases.

What condition is associated with DMPK p.Ala172Val (c.515C>T)?

DMPK p.Ala172Val (c.515C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DMPK p.Ala172Val (c.515C>T) in the general population?

DMPK p.Ala172Val (c.515C>T) is ultra-rare (popmax 0.0201%, eas) (gnomAD).

What do computational predictors say about DMPK p.Ala172Val (c.515C>T)?

AlphaMissense predicts ambiguous (score 0.5135) — an in-silico prediction, not a clinical call.

DMPK p.Ala172Val

c.515C>T · rs199731275 · VCV3083104

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5135 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0201%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5135	ambiguous
REVEL	0.455	indeterminate
SaProt	LLR -10.02	damaging
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 0.75	unconstrained · MANE · 1,766 bp · p 5.9e-05 · regional, not allelic
Overall
CADD	32.0	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 0.0201% East Asian · 9/44,884 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00779%

Overall 0.00112% 18/1,613,966 alleles · ultra-rare exomes 16/1,461,636 · genomes 2/152,330 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0201%	4,987
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0064%	15,627
Finnishnot grpmax-eligible	0.00157%	63,812
European (non-Finnish)	0.000254%	393,340

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.Ala172Val
Coding: c.515C>T
MANE Select: NM_004409
dbSNP: rs199731275
Type: single nucleotide variant
Location: chr19:45778559 (GRCh38)
Gene constraint: LOEUF 0.67 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.91 · 2 PDB
Residue 172: the protein kinase domain; an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DMPK p.Pro257= Likely benign ★★ same condition
DMPK c.161-106C>A Uncertain significance ★ same condition
DMPK c.161-115A>G Uncertain significance ★ same condition
DMPK c.161-123A>C Uncertain significance ★ same condition
DMPK c.161-146G>A Uncertain significance ★ same condition
DMPK c.161-27G>T Uncertain significance ★ same condition
DMPK c.161-48G>C Uncertain significance ★ same condition
DMPK c.161-6C>T Uncertain significance ★ 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-ala172val (accessed [today's date]).

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