Is CYP4V2 p.Arg48Pro (c.143G>C) pathogenic?

CYP4V2 p.Arg48Pro (c.143G>C) is classified Uncertain significance in CYP4V2 (ClinVar, Single submitter, 2 submitters; last evaluated 2022-08-23). AlphaMissense: ambiguous (0.5533); Absent from gnomAD v4.1; Associated with optic atrophy.

What condition is associated with CYP4V2 p.Arg48Pro (c.143G>C)?

CYP4V2 p.Arg48Pro (c.143G>C) is associated with optic atrophy (ClinVar).

How common is CYP4V2 p.Arg48Pro (c.143G>C) in the general population?

CYP4V2 p.Arg48Pro (c.143G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CYP4V2 p.Arg48Pro (c.143G>C)?

AlphaMissense predicts ambiguous (score 0.5533) — an in-silico prediction, not a clinical call.

CYP4V2 p.Arg48Pro

c.143G>C · rs1735998479 · VCV1039750

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5533 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

optic atrophy

Computational evidence

Protein change
AlphaMissense	0.5533	ambiguous
REVEL	0.218	benign-leaning
SaProt	LLR -12.70	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.82	GERP -1.9
Regional constraint	o/e 1.02	unconstrained · MANE · 19 kb · p 0.64 · regional, not allelic
Overall
CADD	21.4	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: CYP4V2
Protein: p.Arg48Pro
Coding: c.143G>C
MANE Select: NM_207352
dbSNP: rs1735998479
Type: single nucleotide variant
Location: chr4:186191966 (GRCh38)
Gene constraint: LOEUF 1.126 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 91.05

Full CYP4V2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

optic atrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CYP4V2 c.1090+1G>C Pathogenic same condition
CYP4V2 c.1091-2A>G Pathogenic/Likely pathogenic ★★ same type
CYP4V2 c.413+1G>A Likely pathogenic ★★ same type
CYP4V2 c.414-1G>A Pathogenic/Likely pathogenic ★★ same type
CYP4V2 c.801+1G>A Pathogenic ★★ same type
CYP4V2 p.Arg232Ter Pathogenic ★★ same type
CYP4V2 p.Arg390Cys Pathogenic ★★ same type
CYP4V2 p.Arg390His Pathogenic/Likely pathogenic ★★ 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/cyp4v2-p-arg48pro (accessed [today's date]).

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