Is PPM1F p.Phe183= (c.549C>T) pathogenic?

PPM1F p.Phe183= (c.549C>T) is classified Likely benign in PPM1F (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-24). Ultra-rare (popmax 0.0643%, eas).

How common is PPM1F p.Phe183= (c.549C>T) in the general population?

PPM1F p.Phe183= (c.549C>T) is ultra-rare (popmax 0.0643%, eas) (gnomAD).

PPM1F p.Phe183=

c.549C>T · rs61752250 · VCV2702693

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0643%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.2	GERP -4.1
Overall
CADD	4.691	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0643% East Asian · 27/41,962 alleles

Filtering AF 0.0453% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0391%

Overall 0.00584% 91/1,558,014 alleles · ultra-rare exomes 80/1,405,802 · genomes 11/152,212 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0897%	1,115
East Asiangrpmax	0.0643%	1,554
Admixed American	0.00571%	17,515
African / African-American	0.00407%	24,565
European (non-Finnish)	0.000348%	287,476

Remaining individuals 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: PPM1F
Protein: p.Phe183=
Coding: c.549C>T
MANE Select: NM_014634
dbSNP: rs61752250
Type: single nucleotide variant
Location: chr22:21934033 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.70
Residue 183: the ppm-type phosphatase domain

Full PPM1F gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PPM1F p.Arg149Gln Uncertain significance ★★ ⚠ same type
PPM1F p.Glu103Lys Uncertain significance ★★ ⚠ same type
PPM1F p.Glu82Lys Uncertain significance ★★ ⚠ same type
PPM1F p.Gly320Arg Uncertain significance ★★ ⚠ same type
PPM1F p.Gly386Glu Uncertain significance ★★ ⚠ same type
PPM1F p.His378Tyr Uncertain significance ★★ ⚠ same type
PPM1F p.Met63Val Uncertain significance ★★ ⚠ same type
PPM1F p.Pro430Leu Uncertain significance ★★ ⚠ same type

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/ppm1f-p-phe183 (accessed [today's date]).

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