Is CYP2J2 p.Phe277Val (c.829T>G) pathogenic?

CYP2J2 p.Phe277Val (c.829T>G) is classified Uncertain significance in CYP2J2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-03). AlphaMissense: ambiguous (0.4599); Ultra-rare (popmax 0.015%, afr).

How common is CYP2J2 p.Phe277Val (c.829T>G) in the general population?

CYP2J2 p.Phe277Val (c.829T>G) is ultra-rare (popmax 0.015%, afr) (gnomAD).

What do computational predictors say about CYP2J2 p.Phe277Val (c.829T>G)?

AlphaMissense predicts ambiguous (score 0.4599) — an in-silico prediction, not a clinical call.

CYP2J2 p.Phe277Val

c.829T>G · rs866946075 · VCV2315927

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4599 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, afr)

Computational evidence

Protein change
AlphaMissense	0.4599	ambiguous
REVEL	0.555	indeterminate
SaProt	LLR -8.38	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.2	GERP 1.9, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 33 kb · p 0.28 · regional, not allelic
Overall
CADD	26.1	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 0.015% African / African-American · 11/73,564 alleles

Filtering AF 0.0083% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00644%

Overall 0.00104% 15/1,444,858 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.015%	6,688
Remaining individualsnot grpmax-eligible	0.00647%	15,462

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.Phe277Val
Coding: c.829T>G
MANE Select: NM_000775
dbSNP: rs866946075
Type: single nucleotide variant
Location: chr1:59909816 (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-phe277val (accessed [today's date]).

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