Is PPM1K p.Phe113= (c.339C>T) pathogenic?

PPM1K p.Phe113= (c.339C>T) is classified Benign in PPM1K (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-27). Low-frequency (popmax 1.14%, nfe); Associated with maple syrup urine disease, mild variant.

What condition is associated with PPM1K p.Phe113= (c.339C>T)?

PPM1K p.Phe113= (c.339C>T) is associated with maple syrup urine disease, mild variant (ClinVar).

How common is PPM1K p.Phe113= (c.339C>T) in the general population?

PPM1K p.Phe113= (c.339C>T) is low-frequency (popmax 1.14%, nfe) (gnomAD).

How is Maple syrup urine disease inherited?

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

PPM1K p.Phe113=

c.339C>T · rs116564150 · VCV473874

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.14%, nfe)

Conditions

maple syrup urine disease, mild variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.8	GERP -4.6
Overall
CADD	6.769	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.14% European (non-Finnish) · 13,395/1,180,006 alleles

Filtering AF 1.12% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.11%

Overall 0.999% 16,124/1,614,138 alleles · low-frequency exomes 14,983/1,461,846 · genomes 1,141/152,292 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	1.54%	65
Finnishnot grpmax-eligible	1.47%	68
European (non-Finnish)grpmax	1.14%	88
Remaining individualsnot grpmax-eligible	0.947%	106
South Asian	0.826%	121
Admixed American	0.448%	223
Middle Eastern	0.445%	225
African / African-American	0.153%	653
Ashkenazi Jewishnot grpmax-eligible	0.0541%	1,850

Amish 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: PPM1K
Protein: p.Phe113=
Coding: c.339C>T
MANE Select: NM_152542
dbSNP: rs116564150
Type: single nucleotide variant
Location: chr4:88278245 (GRCh38)
Gene constraint: LOEUF 0.819 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.07 · 3 PDB
Residue 113: the ppm-type phosphatase domain; a β-strand

Full PPM1K gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

maple syrup urine disease, mild variant — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Maple syrup urine disease (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Worldwide)

Similar variants

PPM1K p.Ala325Val Uncertain significance ★★ ⚠ same condition
PPM1K p.Ala98Thr Uncertain significance ★★ ⚠ same condition
PPM1K p.Arg104Gln Uncertain significance ★★ ⚠ same condition
PPM1K p.Arg110Trp Uncertain significance ★★ ⚠ same condition
PPM1K p.Arg176Cys Uncertain significance ★★ ⚠ same condition
PPM1K p.Arg176Gly Uncertain significance ★★ ⚠ same condition
PPM1K p.Arg196Gln Uncertain significance ★★ ⚠ same condition
PPM1K p.Arg49Trp 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/ppm1k-p-phe113 (accessed [today's date]).

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