Is DMPK p.Ser298Phe (c.893C>T) pathogenic?

DMPK p.Ser298Phe (c.893C>T) is classified Conflicting classifications of pathogenicity in DMPK (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-12-16). AlphaMissense: likely benign (0.1297); Rare (popmax 0.295%, sas); Associated with Inborn genetic diseases.

What condition is associated with DMPK p.Ser298Phe (c.893C>T)?

DMPK p.Ser298Phe (c.893C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DMPK p.Ser298Phe (c.893C>T) in the general population?

DMPK p.Ser298Phe (c.893C>T) is rare (popmax 0.295%, sas) (gnomAD).

What do computational predictors say about DMPK p.Ser298Phe (c.893C>T)?

AlphaMissense predicts likely benign (score 0.1297) — an in-silico prediction, not a clinical call.

DMPK p.Ser298Phe

c.893C>T · VCV3256961

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1297 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.295%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1297	likely benign
REVEL	0.171	moderately benign-leaning
SaProt	LLR -9.10	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP -0.31, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 7,198 bp · p 0.0012 · regional, not allelic
Overall
CADD	24.5	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 0.295% South Asian · 269/91,058 alleles

Filtering AF 0.266% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.255%

Overall 0.02% 322/1,613,424 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.295%	339
Remaining individualsnot grpmax-eligible	0.0256%	3,906
Middle Eastern	0.0165%	6,060
European (non-Finnish)	0.00297%	33,707
African / African-American	0.00133%	75,066

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.Ser298Phe
Coding: c.893C>T
MANE Select: NM_004409
Type: single nucleotide variant
Location: chr19:45777580 (GRCh38)
Gene constraint: LOEUF 0.67 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.91 · 2 PDB
Residue 298: the protein kinase domain

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.Ser298Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-ser298phe (accessed [today's date]).

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