Is CYP4F3 p.Asp300Val (c.899A>T) pathogenic?

CYP4F3 p.Asp300Val (c.899A>T) is classified Uncertain significance in CYP4F3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-22). AlphaMissense: likely pathogenic (0.7869); Ultra-rare (popmax 0.0566%, amr).

How common is CYP4F3 p.Asp300Val (c.899A>T) in the general population?

CYP4F3 p.Asp300Val (c.899A>T) is ultra-rare (popmax 0.0566%, amr) (gnomAD).

What do computational predictors say about CYP4F3 p.Asp300Val (c.899A>T)?

AlphaMissense predicts likely pathogenic (score 0.7869) — an in-silico prediction, not a clinical call.

CYP4F3 p.Asp300Val

c.899A>T · rs201590530 · VCV3079735

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7869 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0566%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7869	likely pathogenic · top 10% in CYP4F3
REVEL	0.809	moderately pathogenic-leaning
SaProt	LLR -18.24	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 18 kb · p 0.14 · regional, not allelic
Overall
CADD	29.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0566% Admixed American · 34/60,024 alleles

Filtering AF 0.0416% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0365%

Overall 0.00229% 37/1,614,160 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0566%	1,765
Remaining individualsnot grpmax-eligible	0.0032%	31,252
African / African-American	0.00133%	75,048

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.Asp300Val
Coding: c.899A>T
MANE Select: NM_000896
dbSNP: rs201590530
Type: single nucleotide variant
Location: chr19:15650164 (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-asp300val (accessed [today's date]).

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