Is CYP4F3 p.Glu387Asp (c.1161G>C) pathogenic?

CYP4F3 p.Glu387Asp (c.1161G>C) is classified Uncertain significance in CYP4F3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-06). AlphaMissense: likely pathogenic (0.9525); Very rare (popmax 0.00267%, afr).

How common is CYP4F3 p.Glu387Asp (c.1161G>C) in the general population?

CYP4F3 p.Glu387Asp (c.1161G>C) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about CYP4F3 p.Glu387Asp (c.1161G>C)?

AlphaMissense predicts likely pathogenic (score 0.9525) — an in-silico prediction, not a clinical call.

CYP4F3 p.Glu387Asp

c.1161G>C · rs1036308305 · VCV3079726

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9525 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9525	likely pathogenic · top 2% in CYP4F3
REVEL	0.898	moderately pathogenic-leaning
SaProt	LLR -8.07	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 1.9, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 18 kb · p 0.14 · regional, not allelic
Overall
CADD	24.0	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 0.00267% African / African-American · 2/74,886 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000558% 9/1,613,988 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,443
Remaining individualsnot grpmax-eligible	0.0016%	62,486
European (non-Finnish)	0.000508%	196,672

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: CYP4F3
Protein: p.Glu387Asp
Coding: c.1161G>C
MANE Select: NM_000896
dbSNP: rs1036308305
Type: single nucleotide variant
Location: chr19:15658309 (GRCh38)
Gene constraint: LOEUF 1.134 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.04

Full CYP4F3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CYP4F3 c.1398-10C>T Benign ★★ same type
CYP4F3 p.Ile173= Likely benign ★★ same type
CYP4F3 p.Met191Val Benign ★★ same type
CYP4F3 p.Val270Ile Benign/Likely benign ★★ ⚠ same type
CYP4F3 p.Val398Ile Benign ★★ same type
CYP4F3 c.199-1688G>A Uncertain significance ★ same type
CYP4F3 c.199-1695A>T Uncertain significance ★ same type
CYP4F3 c.199-1709T>G 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/cyp4f3-p-glu387asp (accessed [today's date]).

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