Is BCO2 p.Ile309Thr (c.926T>C) pathogenic?

BCO2 p.Ile309Thr (c.926T>C) is classified Uncertain significance in BCO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-18). AlphaMissense: ambiguous (0.4146); Ultra-rare (popmax 0.0787%, afr).

How common is BCO2 p.Ile309Thr (c.926T>C) in the general population?

BCO2 p.Ile309Thr (c.926T>C) is ultra-rare (popmax 0.0787%, afr) (gnomAD).

What do computational predictors say about BCO2 p.Ile309Thr (c.926T>C)?

AlphaMissense predicts ambiguous (score 0.4146) — an in-silico prediction, not a clinical call.

BCO2 p.Ile309Thr

c.926T>C · rs183792404 · VCV2363519

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4146 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0787%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4146	ambiguous
REVEL	0.795	moderately pathogenic-leaning
SaProt	LLR -7.05	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 42 kb · p 0.37 · regional, not allelic
Overall
CADD	23.8	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 0.0787% African / African-American · 59/74,972 alleles

Filtering AF 0.0626% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0568%

Overall 0.00496% 80/1,613,780 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0787%	1,271
Remaining individualsnot grpmax-eligible	0.0144%	6,943
Admixed American	0.00501%	19,973
South Asian	0.00439%	22,764
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602
European (non-Finnish)	0.000339%	294,972

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.Ile309Thr
Coding: c.926T>C
MANE Select: NM_031938
dbSNP: rs183792404
Type: single nucleotide variant
Location: chr11:112200673 (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-ile309thr (accessed [today's date]).

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