Is CYP4F2 p.Ala82= (c.246C>T) pathogenic?

CYP4F2 p.Ala82= (c.246C>T) is classified Benign in CYP4F2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-11-15). Common (popmax 18%, mid) — too common for a highly-penetrant pathogenic allele; Associated with CYP4F2-related disorder.

What condition is associated with CYP4F2 p.Ala82= (c.246C>T)?

CYP4F2 p.Ala82= (c.246C>T) is associated with CYP4F2-related disorder (ClinVar).

CYP4F2 p.Ala82=

Q: How common is CYP4F2 p.Ala82= (c.246C>T) in the general population?

CYP4F2 p.Ala82= (c.246C>T) is common (popmax 18%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.246C>T · rs3093114 · VCV3060160

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 18%, mid) — 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 -9.9	GERP 0.72
Overall
CADD	8.569	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 18% Middle Eastern · 1,081/6,008 alleles

Filtering AF 17.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 16.7%

Overall 15.8% 250,920/1,592,672 alleles · common

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	19.7%	5
Middle Easterngrpmax	18%	6
European (non-Finnish)	16.5%	6
Remaining individualsnot grpmax-eligible	15.7%	6
South Asian	15.3%	7
African / African-American	13.5%	7
Admixed American	11.3%	9
Finnishnot grpmax-eligible	11.3%	9
East Asian	10.2%	10
Amishnot grpmax-eligible	9.34%	11

Ashkenazi Jewish 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: CYP4F2
Protein: p.Ala82=
Coding: c.246C>T
MANE Select: NM_001082
dbSNP: rs3093114
Type: single nucleotide variant
Location: chr19:15895603 (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.Ala16Pro 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-ala82 (accessed [today's date]).

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