Is CYP4F2 p.Ala16Pro (c.46G>C) pathogenic?

CYP4F2 p.Ala16Pro (c.46G>C) is classified Benign in CYP4F2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-26). AlphaMissense: likely benign (0.0915); Low-frequency (popmax 1.27%, afr); Associated with CYP4F2-related disorder.

What condition is associated with CYP4F2 p.Ala16Pro (c.46G>C)?

CYP4F2 p.Ala16Pro (c.46G>C) is associated with CYP4F2-related disorder (ClinVar).

How common is CYP4F2 p.Ala16Pro (c.46G>C) in the general population?

CYP4F2 p.Ala16Pro (c.46G>C) is low-frequency (popmax 1.27%, afr) (gnomAD).

What do computational predictors say about CYP4F2 p.Ala16Pro (c.46G>C)?

AlphaMissense predicts likely benign (score 0.0915) — an in-silico prediction, not a clinical call.

CYP4F2 p.Ala16Pro

c.46G>C · rs114099324 · VCV3052405

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0915 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.27%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

CYP4F2-related disorder

Computational evidence

Protein change
AlphaMissense	0.0915	likely benign
REVEL	0.312	indeterminate
SaProt	LLR -7.95	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.4	GERP -3
Regional constraint	o/e 0.90	unconstrained · MANE · 19 kb · p 0.0078 · regional, not allelic
Overall
CADD	14.6	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 1.27% African / African-American · 954/75,026 alleles

Filtering AF 1.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.18%

Overall 0.071% 1,146/1,613,954 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.27%	79
Admixed American	0.162%	619
Middle Eastern	0.149%	673
Remaining individualsnot grpmax-eligible	0.0976%	1,025
European (non-Finnish)	0.00203%	49,165
South Asian	0.0011%	91,068

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.Ala16Pro
Coding: c.46G>C
MANE Select: NM_001082
dbSNP: rs114099324
Type: single nucleotide variant
Location: chr19:15897566 (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 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.Ala82= Benign same condition
CYP4F2 p.Arg275= Likely benign same condition
CYP4F2 p.Arg490= Likely benign same condition
CYP4F2 p.Arg515= 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-ala16pro (accessed [today's date]).

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