Is CYP2B6 p.Ile245Val (c.733A>G) pathogenic?

CYP2B6 p.Ile245Val (c.733A>G) is classified Uncertain significance in CYP2B6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-14). AlphaMissense: likely benign (0.1082); Very rare (popmax 0.00314%, nfe).

How common is CYP2B6 p.Ile245Val (c.733A>G) in the general population?

CYP2B6 p.Ile245Val (c.733A>G) is very rare (popmax 0.00314%, nfe) (gnomAD).

What do computational predictors say about CYP2B6 p.Ile245Val (c.733A>G)?

AlphaMissense predicts likely benign (score 0.1082) — an in-silico prediction, not a clinical call.

CYP2B6 p.Ile245Val

c.733A>G · VCV3837831

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1082 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00314%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1082	likely benign
REVEL	0.088	moderately benign-leaning
SaProt	LLR -6.86	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.65	phastCons 0.001
Regional constraint	o/e 0.99	unconstrained · MANE · 26 kb · p 0.73 · regional, not allelic
Overall
CADD	0.423	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 0.00314% European (non-Finnish) · 37/1,179,312 alleles

Filtering AF 0.00232% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00202%

Overall 0.00242% 39/1,612,710 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00314%	31,873
Admixed American	0.00167%	59,870
Remaining individualsnot grpmax-eligible	0.0016%	62,442

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: CYP2B6
Protein: p.Ile245Val
Coding: c.733A>G
MANE Select: NM_000767
Type: single nucleotide variant
Location: chr19:41009306 (GRCh38)
Gene constraint: LOEUF 1.044 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.25 · 13 PDB
Residue 245: an α-helix

Full CYP2B6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CYP2B6 p.Lys139Glu Likely benign ★★ ⚠ same type
CYP2B6 p.Lys262Arg Benign ★★ same type
CYP2B6 p.Ala102Ser Uncertain significance ★ ⚠ same type
CYP2B6 p.Ala243Ser Uncertain significance ★ ⚠ same type
CYP2B6 p.Ala260Thr Uncertain significance ★ ⚠ same type
CYP2B6 p.Arg158Trp Uncertain significance ★ ⚠ same type
CYP2B6 p.Arg336His Uncertain significance ★ ⚠ same type
CYP2B6 p.Arg336Pro 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/cyp2b6-p-ile245val (accessed [today's date]).

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