Is CYP4V2 p.Ser341Pro (c.1021T>C) pathogenic?

CYP4V2 p.Ser341Pro (c.1021T>C) is classified Pathogenic in CYP4V2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2012-04-12). AlphaMissense: likely pathogenic (0.9528); Very rare (popmax 0.00133%, afr); Associated with Bietti crystalline corneoretinal dystrophy.

What condition is associated with CYP4V2 p.Ser341Pro (c.1021T>C)?

CYP4V2 p.Ser341Pro (c.1021T>C) is associated with Bietti crystalline corneoretinal dystrophy (ClinVar).

How common is CYP4V2 p.Ser341Pro (c.1021T>C) in the general population?

CYP4V2 p.Ser341Pro (c.1021T>C) is very rare (popmax 0.00133%, afr) (gnomAD).

How is Bietti crystalline dystrophy inherited?

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

What do computational predictors say about CYP4V2 p.Ser341Pro (c.1021T>C)?

AlphaMissense predicts likely pathogenic (score 0.9528) — an in-silico prediction, not a clinical call.

CYP4V2 p.Ser341Pro

c.1021T>C · rs199476199 · VCV39249

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9528 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Bietti crystalline corneoretinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.9528	likely pathogenic ✓ concordant with ClinVar
REVEL	0.559	indeterminate
SaProt	LLR -12.68	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.3	GERP -4.5
Regional constraint	o/e 1.02	unconstrained · MANE · 19 kb · p 0.64 · regional, not allelic
Overall
CADD	20.4	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

Grpmax group 0.00133% African / African-American · 1/75,068 alleles

Overall 6.84e-05% 1/1,461,890 alleles · very rare

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.Ser341Pro
Coding: c.1021T>C
MANE Select: NM_207352
dbSNP: rs199476199
Type: single nucleotide variant
Location: chr4:186205233 (GRCh38)
Gene constraint: LOEUF 1.126 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 91.05
Residue 341: a UniProt-annotated variant site (in bcd)

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

For Bietti crystalline dystrophy (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult

Similar variants

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
CYP4V2 p.Arg400His Pathogenic/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-ser341pro (accessed [today's date]).

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