Is CYP4F8 p.Ser7Pro (c.19T>C) pathogenic?

CYP4F8 p.Ser7Pro (c.19T>C) is classified Uncertain significance in CYP4F8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-23). AlphaMissense: likely benign (0.0663); Absent from gnomAD v4.1.

How common is CYP4F8 p.Ser7Pro (c.19T>C) in the general population?

CYP4F8 p.Ser7Pro (c.19T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CYP4F8 p.Ser7Pro (c.19T>C)?

AlphaMissense predicts likely benign (score 0.0663) — an in-silico prediction, not a clinical call.

CYP4F8 p.Ser7Pro

c.19T>C · VCV3838007

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0663 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0663	likely benign
REVEL	0.104	moderately benign-leaning
SaProt	LLR -6.82	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.57
Regional constraint	o/e 1.00	unconstrained · MANE · 14 kb · p 0.93 · regional, not allelic
Overall
CADD	17.91	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

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.Ser7Pro
Coding: c.19T>C
MANE Select: NM_007253
Type: single nucleotide variant
Location: chr19:15615635 (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-ser7pro (accessed [today's date]).

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