Is BCO1 p.Gly36Arg (c.106G>A) pathogenic?

BCO1 p.Gly36Arg (c.106G>A) is classified Uncertain significance in BCO1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-21). AlphaMissense: likely pathogenic (0.9781); Ultra-rare (popmax 0.0143%, nfe).

How common is BCO1 p.Gly36Arg (c.106G>A) in the general population?

BCO1 p.Gly36Arg (c.106G>A) is ultra-rare (popmax 0.0143%, nfe) (gnomAD).

What do computational predictors say about BCO1 p.Gly36Arg (c.106G>A)?

AlphaMissense predicts likely pathogenic (score 0.9781) — an in-silico prediction, not a clinical call.

BCO1 p.Gly36Arg

c.106G>A · rs772224825 · VCV3133523

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9781 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0143%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9781	likely pathogenic · top 2% in BCO1
REVEL	0.965	strongly pathogenic-leaning
SaProt	LLR -15.98	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 52 kb · p 2.8e-05 · regional, not allelic
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0143% European (non-Finnish) · 169/1,179,678 alleles

Filtering AF 0.0125% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0119%

Overall 0.011% 177/1,613,598 alleles · ultra-rare exomes 170/1,461,408 · genomes 7/152,190 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0143%	6,980
East Asian	0.00445%	22,447
African / African-American	0.00267%	37,453
South Asian	0.0022%	45,529
Admixed American	0.00167%	59,976
Remaining individualsnot grpmax-eligible	0.0016%	62,462

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.Gly36Arg
Coding: c.106G>A
MANE Select: NM_017429
dbSNP: rs772224825
Type: single nucleotide variant
Location: chr16:81245516 (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 type
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-gly36arg (accessed [today's date]).

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