Is BCO2 p.Asn81Ser (c.242A>G) pathogenic?

BCO2 p.Asn81Ser (c.242A>G) is classified Uncertain significance in BCO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-06). AlphaMissense: likely benign (0.0622); Ultra-rare (popmax 0.0329%, mid).

How common is BCO2 p.Asn81Ser (c.242A>G) in the general population?

BCO2 p.Asn81Ser (c.242A>G) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

What do computational predictors say about BCO2 p.Asn81Ser (c.242A>G)?

AlphaMissense predicts likely benign (score 0.0622) — an in-silico prediction, not a clinical call.

BCO2 p.Asn81Ser

c.242A>G · VCV3480276

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0622 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0622	likely benign
REVEL	0.224	benign-leaning
SaProt	LLR -6.80	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 -0.049	GERP -1.7
Regional constraint	o/e 0.97	unconstrained · MANE · 42 kb · p 0.37 · regional, not allelic
Overall
CADD	12.42	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

Grpmax group 0.0329% Middle Eastern · 2/6,084 alleles

Filtering AF 0.009% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00681%

Overall 0.00211% 34/1,614,074 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,042
Admixed American	0.0167%	6,001
South Asian	0.00768%	13,013
African / African-American	0.00133%	74,930
European (non-Finnish)	0.00119%	84,288

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.Asn81Ser
Coding: c.242A>G
MANE Select: NM_031938
Type: single nucleotide variant
Location: chr11:112179431 (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-asn81ser (accessed [today's date]).

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