Is CYP4V2 p.Ser482= (c.1446G>A) pathogenic?

CYP4V2 p.Ser482= (c.1446G>A) is classified Conflicting classifications of pathogenicity in CYP4V2 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-15). Rare (popmax 0.802%, eas); Associated with corneal dystrophy.

What condition is associated with CYP4V2 p.Ser482= (c.1446G>A)?

CYP4V2 p.Ser482= (c.1446G>A) is associated with corneal dystrophy, Bietti crystalline corneoretinal dystrophy, inherited retinal dystrophy (ClinVar).

How common is CYP4V2 p.Ser482= (c.1446G>A) in the general population?

CYP4V2 p.Ser482= (c.1446G>A) is rare (popmax 0.802%, eas) (gnomAD).

CYP4V2 p.Ser482=

c.1446G>A · rs141950964 · VCV193951

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.802%, eas)

Conditions

corneal 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 -0.076	GERP -2.8, phastCons 0.54
Overall
CADD	2.009	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.802% East Asian · 360/44,876 alleles

Filtering AF 0.734% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.707%

Overall 0.0322% 520/1,614,154 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.802%	125
Remaining individualsnot grpmax-eligible	0.122%	822
African / African-American	0.0187%	5,361
Admixed American	0.0167%	6,003
South Asian	0.0143%	7,006
European (non-Finnish)	0.0039%	25,653
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,600

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.Ser482=
Coding: c.1446G>A
MANE Select: NM_207352
dbSNP: rs141950964
Type: single nucleotide variant
Location: chr4:186210509 (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

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

Also linked: Bietti crystalline corneoretinal dystrophy inherited retinal dystrophy

Similar variants

CYP4V2 p.Ser482Ter Pathogenic same residue
CYP4V2 p.Ser482Ala Uncertain significance ★ ⚠ same residue
CYP4V2 p.Ser482Leu Uncertain significance ★ ⚠ same residue
CYP4V2 p.Ser482Pro 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

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-ser482 (accessed [today's date]).

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