Is CYP2C8 p.Ser336Arg (c.1008C>A) pathogenic?

CYP2C8 p.Ser336Arg (c.1008C>A) is classified Uncertain significance in CYP2C8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-01). AlphaMissense: likely benign (0.2615); Absent from gnomAD v4.1.

How common is CYP2C8 p.Ser336Arg (c.1008C>A) in the general population?

CYP2C8 p.Ser336Arg (c.1008C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CYP2C8 p.Ser336Arg (c.1008C>A)?

AlphaMissense predicts likely benign (score 0.2615) — an in-silico prediction, not a clinical call.

CYP2C8 p.Ser336Arg

c.1008C>A · VCV4236868

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2615 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2615	likely benign
REVEL	0.046	moderately benign-leaning
SaProt	LLR -9.55	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 -5.2	GERP -0.78
Regional constraint	o/e 1.12	unconstrained · MANE · 32 kb · p 0.0032 · regional, not allelic
Overall
CADD	9.543	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CYP2C8
Protein: p.Ser336Arg
Coding: c.1008C>A
MANE Select: NM_000770
Type: single nucleotide variant
Location: chr10:95043031 (GRCh38)
Gene constraint: LOEUF 1.502 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.07 · 5 PDB

Full CYP2C8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CYP2C8 c.168+669A>G Benign ★★ same type
CYP2C8 p.His353= Benign ★★ same type
CYP2C8 p.Val181Ile Benign ★★ same type
CYP2C8 p.Ala253Pro Uncertain significance ★ ⚠ same type
CYP2C8 p.Arg200Lys Uncertain significance ★ ⚠ same type
CYP2C8 p.Asn133Asp Uncertain significance ★ ⚠ same type
CYP2C8 p.Asn176Ser Uncertain significance ★ ⚠ same type
CYP2C8 p.Asn176Thr 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/cyp2c8-p-ser336arg (accessed [today's date]).

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