Is CYP4F22 p.Arg41Pro (c.122G>C) pathogenic?

CYP4F22 p.Arg41Pro (c.122G>C) is classified Uncertain significance in CYP4F22 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-03). AlphaMissense: likely benign (0.1641); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CYP4F22 p.Arg41Pro (c.122G>C)?

CYP4F22 p.Arg41Pro (c.122G>C) is associated with Inborn genetic diseases (ClinVar).

How common is CYP4F22 p.Arg41Pro (c.122G>C) in the general population?

CYP4F22 p.Arg41Pro (c.122G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CYP4F22 p.Arg41Pro (c.122G>C)?

AlphaMissense predicts likely benign (score 0.1641) — an in-silico prediction, not a clinical call.

CYP4F22 p.Arg41Pro

c.122G>C · VCV3837984

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1641 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1641	likely benign
REVEL	0.349	indeterminate
SaProt	LLR -9.61	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.6	GERP -2.6
Regional constraint	o/e 0.94	unconstrained · MANE · 19 kb · p 0.2 · regional, not allelic
Overall
CADD	2.443	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: CYP4F22
Protein: p.Arg41Pro
Coding: c.122G>C
MANE Select: NM_173483
Type: single nucleotide variant
Location: chr19:15525458 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.59

Full CYP4F22 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CYP4F22 p.Arg41Trp Uncertain significance ★ ⚠ same residue
CYP4F22 p.Arg41= Likely benign ★ same residue
CYP4F22 p.Arg154Trp Uncertain significance ★★ ⚠ same condition
CYP4F22 p.Arg57Cys Uncertain significance ★★ ⚠ same condition
CYP4F22 p.Asp338Asn Uncertain significance ★★ ⚠ same condition
CYP4F22 p.Gly290Trp Uncertain significance ★★ ⚠ same condition
CYP4F22 p.Tyr432Cys Uncertain significance ★★ ⚠ same condition
CYP4F22 p.Ala124Ser Uncertain significance ★ ⚠ same condition

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/cyp4f22-p-arg41pro (accessed [today's date]).

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