Is BCO2 p.Met238Leu (c.712A>C) pathogenic?

BCO2 p.Met238Leu (c.712A>C) is classified Uncertain significance in BCO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-14). AlphaMissense: likely benign (0.1514); Absent from gnomAD v4.1.

How common is BCO2 p.Met238Leu (c.712A>C) in the general population?

BCO2 p.Met238Leu (c.712A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BCO2 p.Met238Leu (c.712A>C)?

AlphaMissense predicts likely benign (score 0.1514) — an in-silico prediction, not a clinical call.

BCO2 p.Met238Leu

c.712A>C · rs765749418 · VCV2334879

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1514 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1514	likely benign
REVEL	0.649	pathogenic-leaning
SaProt	LLR -5.95	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP -1.7, phastCons 0.99
Regional constraint	o/e 0.97	unconstrained · MANE · 42 kb · p 0.37 · regional, not allelic
Overall
CADD	21.1	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

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: BCO2
Protein: p.Met238Leu
Coding: c.712A>C
MANE Select: NM_031938
dbSNP: rs765749418
Type: single nucleotide variant
Location: chr11:112194731 (GRCh38)
Gene constraint: LOEUF 1.047 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.41

Full BCO2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BCO2 p.Arg472Ter Likely benign ★★ same type
BCO2 p.Ala115Val Uncertain significance ★ ⚠ same type
BCO2 p.Ala223Gly Uncertain significance ★ ⚠ same type
BCO2 p.Ala318Val Uncertain significance ★ ⚠ same type
BCO2 p.Ala437Ser Uncertain significance ★ ⚠ same type
BCO2 p.Arg184Trp Uncertain significance ★ ⚠ same type
BCO2 p.Arg253Gln Uncertain significance ★ ⚠ same type
BCO2 p.Arg27Trp 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/bco2-p-met238leu (accessed [today's date]).

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