Is CYP4V2 p.Ser347Pro (c.1039T>C) pathogenic?

CYP4V2 p.Ser347Pro (c.1039T>C) is classified Uncertain significance in CYP4V2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-15). AlphaMissense: likely pathogenic (0.8853); Very rare (popmax 0.00333%, amr); Associated with Inborn genetic diseases.

What condition is associated with CYP4V2 p.Ser347Pro (c.1039T>C)?

CYP4V2 p.Ser347Pro (c.1039T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CYP4V2 p.Ser347Pro (c.1039T>C) in the general population?

CYP4V2 p.Ser347Pro (c.1039T>C) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about CYP4V2 p.Ser347Pro (c.1039T>C)?

AlphaMissense predicts likely pathogenic (score 0.8853) — an in-silico prediction, not a clinical call.

CYP4V2 p.Ser347Pro

c.1039T>C · VCV4009034

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8853 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8853	likely pathogenic
REVEL	0.304	indeterminate
SaProt	LLR -10.40	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP -0.091, phastCons 0.53
Regional constraint	o/e 1.02	unconstrained · MANE · 19 kb · p 0.64 · regional, not allelic
Overall
CADD	22.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Grpmax group 0.00333% Admixed American · 2/60,026 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000137% 2/1,461,890 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.Ser347Pro
Coding: c.1039T>C
MANE Select: NM_207352
Type: single nucleotide variant
Location: chr4:186205251 (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

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

Similar variants

CYP4V2 p.Ser347Cys Uncertain significance ★ ⚠ same residue
CYP4V2 p.Ala101Val Uncertain significance ★★ ⚠ same condition
CYP4V2 p.Ala185Glu Uncertain significance ★★ ⚠ same condition
CYP4V2 p.Ala25Thr Uncertain significance ★★ ⚠ same condition
CYP4V2 p.Ala370Thr Uncertain significance ★★ ⚠ same condition
CYP4V2 p.Ala456Gly Uncertain significance ★★ ⚠ same condition
CYP4V2 p.Arg221His Uncertain significance ★★ ⚠ same condition
CYP4V2 p.Asn104Asp 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/cyp4v2-p-ser347pro (accessed [today's date]).

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