Is CYP4F2 p.Pro55= (c.165A>G) pathogenic?

CYP4F2 p.Pro55= (c.165A>G) is classified Benign in CYP4F2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-11-15). Common (popmax 31.4%, afr) — too common for a highly-penetrant pathogenic allele; Associated with CYP4F2-related disorder.

What condition is associated with CYP4F2 p.Pro55= (c.165A>G)?

CYP4F2 p.Pro55= (c.165A>G) is associated with CYP4F2-related disorder (ClinVar).

CYP4F2 p.Pro55=

Q: How common is CYP4F2 p.Pro55= (c.165A>G) in the general population?

CYP4F2 p.Pro55= (c.165A>G) is common (popmax 31.4%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.165A>G · rs3093106 · VCV3060298

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 31.4%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

CYP4F2-related disorder

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 -20	GERP -3
Overall
CADD	0.347	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 31.4% African / African-American · 23,497/74,740 alleles

Filtering AF 31.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 31%

Overall 16.9% 273,211/1,613,120 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	31.4%	3
Ashkenazi Jewishnot grpmax-eligible	21.5%	5
Middle Eastern	19.8%	5
Remaining individualsnot grpmax-eligible	17.4%	6
European (non-Finnish)	16.6%	6
South Asian	16.4%	6
Admixed American	13.4%	7
Finnishnot grpmax-eligible	11.3%	9
East Asian	10.5%	10
Amishnot grpmax-eligible	9.32%	11

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: CYP4F2
Protein: p.Pro55=
Coding: c.165A>G
MANE Select: NM_001082
dbSNP: rs3093106
Type: single nucleotide variant
Location: chr19:15897447 (GRCh38)
Gene constraint: LOEUF 1.197 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.97

Full CYP4F2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CYP4F2-related disorder

Similar variants

CYP4F2 p.Pro55Leu Uncertain significance ★ ⚠ same residue
CYP4F2 c.1398-4C>G Benign same condition
CYP4F2 c.343+6A>G Likely benign same condition
CYP4F2 c.919-9T>G Likely benign same condition
CYP4F2 c.*8A>G Likely benign same condition
CYP4F2 p.Ala16Pro Benign ⚠ same condition
CYP4F2 p.Ala82= Benign same condition
CYP4F2 p.Arg275= Likely benign 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/cyp4f2-p-pro55 (accessed [today's date]).

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