Is CYP2J2 p.Pro112= (c.336C>T) pathogenic?

CYP2J2 p.Pro112= (c.336C>T) is classified Likely benign in CYP2J2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-01). Rare (popmax 0.33%, mid).

How common is CYP2J2 p.Pro112= (c.336C>T) in the general population?

CYP2J2 p.Pro112= (c.336C>T) is rare (popmax 0.33%, mid) (gnomAD).

CYP2J2 p.Pro112=

c.336C>T · rs138732194 · VCV2638851

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.33%, mid)

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 -12	GERP -3.8
Overall
CADD	0.435	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.33% Middle Eastern · 20/6,056 alleles

Filtering AF 0.279% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.276%

Overall 0.264% 4,256/1,613,866 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.03%	97
Remaining individualsnot grpmax-eligible	0.402%	249
Middle Easterngrpmax	0.33%	303
European (non-Finnish)	0.287%	348
Amishnot grpmax-eligible	0.219%	456
South Asian	0.206%	484
Admixed American	0.0917%	1,091
African / African-American	0.0507%	1,973
Finnishnot grpmax-eligible	0.00937%	10,669
East Asian	0.00223%	44,864

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro112=
Coding: c.336C>T
MANE Select: NM_000775
dbSNP: rs138732194
Type: single nucleotide variant
Location: chr1:59915975 (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-pro112 (accessed [today's date]).

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