Is BCO2 p.His357Tyr (c.1069C>T) pathogenic?

BCO2 p.His357Tyr (c.1069C>T) is classified Uncertain significance in BCO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-12). AlphaMissense: likely pathogenic (0.8771); Ultra-rare (popmax 0.0841%, afr).

How common is BCO2 p.His357Tyr (c.1069C>T) in the general population?

BCO2 p.His357Tyr (c.1069C>T) is ultra-rare (popmax 0.0841%, afr) (gnomAD).

What do computational predictors say about BCO2 p.His357Tyr (c.1069C>T)?

AlphaMissense predicts likely pathogenic (score 0.8771) — an in-silico prediction, not a clinical call.

BCO2 p.His357Tyr

c.1069C>T · rs147138798 · VCV2589684

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8771 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0841%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8771	likely pathogenic · top 9% in BCO2
REVEL	0.935	strongly pathogenic-leaning
SaProt	LLR -9.85	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 42 kb · p 0.37 · 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 0.0841% African / African-American · 63/74,918 alleles

Filtering AF 0.0675% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0614%

Overall 0.00447% 72/1,612,248 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0841%	1,189
Admixed American	0.01%	9,953
Remaining individualsnot grpmax-eligible	0.0032%	31,213
European (non-Finnish)	8.48e-05%	1,179,222

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: BCO2
Protein: p.His357Tyr
Coding: c.1069C>T
MANE Select: NM_031938
dbSNP: rs147138798
Type: single nucleotide variant
Location: chr11:112202065 (GRCh38)
Gene constraint: LOEUF 1.047 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.41
Residue 357: a binding site

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-his357tyr (accessed [today's date]).

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