Is CYP4F8 p.Arg47Cys (c.139C>T) pathogenic?

CYP4F8 p.Arg47Cys (c.139C>T) is classified Uncertain significance in CYP4F8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-22). AlphaMissense: likely benign (0.1265); Very rare (popmax 0.00446%, eas).

How common is CYP4F8 p.Arg47Cys (c.139C>T) in the general population?

CYP4F8 p.Arg47Cys (c.139C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about CYP4F8 p.Arg47Cys (c.139C>T)?

AlphaMissense predicts likely benign (score 0.1265) — an in-silico prediction, not a clinical call.

CYP4F8 p.Arg47Cys

c.139C>T · VCV3270687

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1265 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1265	likely benign
REVEL	0.216	benign-leaning
SaProt	LLR -8.78	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 -0.99
Regional constraint	o/e 1.00	unconstrained · MANE · 14 kb · p 0.93 · regional, not allelic
Overall
CADD	16.81	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

Grpmax group 0.00446% East Asian · 2/44,862 alleles

Filtering AF 0.00215% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00191%

Overall 0.00291% 47/1,613,934 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,431
South Asian	0.00439%	22,772
Admixed American	0.00333%	29,999
European (non-Finnish)	0.00297%	33,713
African / African-American	0.00267%	37,459
Remaining individualsnot grpmax-eligible	0.0016%	62,480
Finnishnot grpmax-eligible	0.00156%	64,036

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: CYP4F8
Protein: p.Arg47Cys
Coding: c.139C>T
MANE Select: NM_007253
Type: single nucleotide variant
Location: chr19:15615755 (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.Arg47His Uncertain significance ★ ⚠ same residue
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

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-arg47cys (accessed [today's date]).

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