Is BCO1 p.Arg266Gln (c.797G>A) pathogenic?

BCO1 p.Arg266Gln (c.797G>A) is classified Uncertain significance in BCO1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-31). AlphaMissense: likely benign (0.1452); Ultra-rare (popmax 0.0254%, afr).

How common is BCO1 p.Arg266Gln (c.797G>A) in the general population?

BCO1 p.Arg266Gln (c.797G>A) is ultra-rare (popmax 0.0254%, afr) (gnomAD).

What do computational predictors say about BCO1 p.Arg266Gln (c.797G>A)?

AlphaMissense predicts likely benign (score 0.1452) — an in-silico prediction, not a clinical call.

BCO1 p.Arg266Gln

c.797G>A · VCV3260709

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1452 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0254%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1452	likely benign
REVEL	0.734	pathogenic-leaning
SaProt	LLR -9.07	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.5	GERP 1.5, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 52 kb · p 2.8e-05 · regional, not allelic
Overall
CADD	24.9	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 0.0254% African / African-American · 19/74,852 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0137%

Overall 0.013% 210/1,612,362 alleles · ultra-rare exomes 193/1,460,352 · genomes 17/152,010 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0254%	3,940
Admixed American	0.025%	3,998
Middle Eastern	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.016%	6,248
European (non-Finnish)	0.0137%	7,284
South Asian	0.0022%	45,533
Finnishnot grpmax-eligible	0.0016%	62,498

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: BCO1
Protein: p.Arg266Gln
Coding: c.797G>A
MANE Select: NM_017429
Type: single nucleotide variant
Location: chr16:81268085 (GRCh38)
Gene constraint: LOEUF 1.17 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.03

Full BCO1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BCO1 p.Arg266Trp Uncertain significance ★★ ⚠ same residue
BCO1 p.Thr170Met Uncertain significance ★★ ⚠ same type
BCO1 c.1101+48C>T Benign ★★ same type
BCO1 c.1102-81T>C Benign ★★ same type
BCO1 c.1303-13G>A Benign ★★ same type
BCO1 c.1303-70A>G Benign ★★ same type
BCO1 c.194-219A>G Benign ★★ same type
BCO1 c.194-74A>G Benign ★★ 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/bco1-p-arg266gln (accessed [today's date]).

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