Is CYP4F8 p.Pro162Leu (c.485C>T) pathogenic?

CYP4F8 p.Pro162Leu (c.485C>T) is classified Uncertain significance in CYP4F8 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-02). AlphaMissense: likely benign (0.1741); Absent from gnomAD v4.1.

How common is CYP4F8 p.Pro162Leu (c.485C>T) in the general population?

CYP4F8 p.Pro162Leu (c.485C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CYP4F8 p.Pro162Leu (c.485C>T)?

AlphaMissense predicts likely benign (score 0.1741) — an in-silico prediction, not a clinical call.

CYP4F8 p.Pro162Leu

c.485C>T · rs763867629 · VCV3079737

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1741 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1741	likely benign
REVEL	0.158	moderately benign-leaning
SaProt	LLR -12.42	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.86
Regional constraint	o/e 1.00	unconstrained · MANE · 14 kb · p 0.93 · regional, not allelic
Overall
CADD	22.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CYP4F8
Protein: p.Pro162Leu
Coding: c.485C>T
MANE Select: NM_007253
dbSNP: rs763867629
Type: single nucleotide variant
Location: chr19:15619722 (GRCh38)
Gene constraint: LOEUF 1.232 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.45

Full CYP4F8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CYP4F8 p.Ala269Val Uncertain significance ★ ⚠ same type
CYP4F8 p.Ala40Asp Uncertain significance ★ ⚠ same type
CYP4F8 p.Arg108Gln Uncertain significance ★ ⚠ same type
CYP4F8 p.Arg145Ile Uncertain significance ★ ⚠ same type
CYP4F8 p.Arg241Gln Uncertain significance ★ ⚠ same type
CYP4F8 p.Arg33His Uncertain significance ★ ⚠ same type
CYP4F8 p.Arg46Cys Uncertain significance ★ ⚠ same type
CYP4F8 p.Arg46His 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/cyp4f8-p-pro162leu (accessed [today's date]).

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