Is CYP2J2 p.Ala14Pro (c.40G>C) pathogenic?

CYP2J2 p.Ala14Pro (c.40G>C) is classified Uncertain significance in CYP2J2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-16). AlphaMissense: likely benign (0.1811); Very rare (popmax 0.00667%, afr).

How common is CYP2J2 p.Ala14Pro (c.40G>C) in the general population?

CYP2J2 p.Ala14Pro (c.40G>C) is very rare (popmax 0.00667%, afr) (gnomAD).

What do computational predictors say about CYP2J2 p.Ala14Pro (c.40G>C)?

AlphaMissense predicts likely benign (score 0.1811) — an in-silico prediction, not a clinical call.

CYP2J2 p.Ala14Pro

c.40G>C · rs141303570 · VCV3079569

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1811 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1811	likely benign
REVEL	0.129	moderately benign-leaning
SaProt	LLR -7.06	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.1	GERP -3.7
Regional constraint	o/e 1.04	unconstrained · MANE · 33 kb · p 0.28 · regional, not allelic
Overall
CADD	6.582	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00667% African / African-American · 5/74,942 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.00031% 5/1,613,382 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: CYP2J2
Protein: p.Ala14Pro
Coding: c.40G>C
MANE Select: NM_000775
dbSNP: rs141303570
Type: single nucleotide variant
Location: chr1:59926707 (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.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
CYP2J2 p.Arg117Gln 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-ala14pro (accessed [today's date]).

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