Is CYP2J2 p.Pro45Leu (c.134C>T) pathogenic?

CYP2J2 p.Pro45Leu (c.134C>T) is classified Uncertain significance in CYP2J2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-24). AlphaMissense: ambiguous (0.3406); Ultra-rare (popmax 0.0134%, eas).

How common is CYP2J2 p.Pro45Leu (c.134C>T) in the general population?

CYP2J2 p.Pro45Leu (c.134C>T) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

What do computational predictors say about CYP2J2 p.Pro45Leu (c.134C>T)?

AlphaMissense predicts ambiguous (score 0.3406) — an in-silico prediction, not a clinical call.

CYP2J2 p.Pro45Leu

c.134C>T · VCV3837884

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3406 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3406	ambiguous
REVEL	0.659	pathogenic-leaning
SaProt	LLR -14.15	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 33 kb · p 0.28 · regional, not allelic
Overall
CADD	29.6	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 0.0134% East Asian · 6/44,898 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.000434% 7/1,614,114 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,483
African / African-American	0.00133%	74,948

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: CYP2J2
Protein: p.Pro45Leu
Coding: c.134C>T
MANE Select: NM_000775
Type: single nucleotide variant
Location: chr1:59926613 (GRCh38)
Gene constraint: LOEUF 1.061 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.90

Full CYP2J2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CYP2J2 p.His103= Benign ★★ same type
CYP2J2 p.Val499= Benign ★★ same type
CYP2J2 p.Ala133Thr Uncertain significance ★ ⚠ same type
CYP2J2 p.Ala14Pro Uncertain significance ★ ⚠ same type
CYP2J2 p.Ala163Thr Uncertain significance ★ ⚠ same type
CYP2J2 p.Ala454Ser Uncertain significance ★ ⚠ same type
CYP2J2 p.Ala4Glu Uncertain significance ★ ⚠ same type
CYP2J2 p.Ala9Ser Uncertain significance ★ ⚠ 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/cyp2j2-p-pro45leu (accessed [today's date]).

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