Is CYP4V2 p.Cys282= (c.846T>C) pathogenic?

CYP4V2 p.Cys282= (c.846T>C) is classified Benign in CYP4V2 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-03). Common (popmax 32.7%, eas) — too common for a highly-penetrant pathogenic allele; Associated with Bietti crystalline corneoretinal dystrophy.

What condition is associated with CYP4V2 p.Cys282= (c.846T>C)?

CYP4V2 p.Cys282= (c.846T>C) is associated with Bietti crystalline corneoretinal dystrophy, corneal dystrophy, inherited retinal dystrophy (ClinVar).

How is Bietti crystalline dystrophy inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CYP4V2 p.Cys282=

Q: How common is CYP4V2 p.Cys282= (c.846T>C) in the general population?

CYP4V2 p.Cys282= (c.846T>C) is common (popmax 32.7%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.846T>C · rs3736456 · VCV166977

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Common

common (popmax 32.7%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

Bietti crystalline corneoretinal dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.1	GERP -4.7
Overall
CADD	0.171	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 32.7% East Asian · 14,676/44,844 alleles

Filtering AF 32.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 32.1%

Overall 7.52% 121,411/1,614,064 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	32.7%	3
Admixed American	21.1%	5
South Asian	16%	6
Middle Eastern	13.9%	7
Ashkenazi Jewishnot grpmax-eligible	13.3%	7
Remaining individualsnot grpmax-eligible	9.25%	11
Finnishnot grpmax-eligible	9.07%	11
Amishnot grpmax-eligible	7.46%	13
African / African-American	6.37%	16
European (non-Finnish)	4.94%	20

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: CYP4V2
Protein: p.Cys282=
Coding: c.846T>C
MANE Select: NM_207352
dbSNP: rs3736456
Type: single nucleotide variant
Location: chr4:186201201 (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

Bietti crystalline corneoretinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: corneal dystrophy inherited retinal dystrophy

For Bietti crystalline dystrophy (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult

Similar variants

CYP4V2 p.Cys282Tyr Uncertain significance ★ same residue
CYP4V2 c.1091-2A>G Pathogenic/Likely pathogenic ★★ same condition
CYP4V2 c.414-1G>A Pathogenic/Likely pathogenic ★★ same condition
CYP4V2 c.801+1G>A Pathogenic ★★ same condition
CYP4V2 p.Arg232Ter Pathogenic ★★ same condition
CYP4V2 p.Arg390Cys Pathogenic ★★ same condition
CYP4V2 p.Arg390His Pathogenic/Likely pathogenic ★★ same condition
CYP4V2 p.Arg390Leu Likely pathogenic ★★ 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/cyp4v2-p-cys282 (accessed [today's date]).

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