Is BCO2 p.Arg472Ter (c.1414C>T) pathogenic?

BCO2 p.Arg472Ter (c.1414C>T) is classified Likely benign in BCO2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-01-19). Rare (popmax 0.585%, afr).

How common is BCO2 p.Arg472Ter (c.1414C>T) in the general population?

BCO2 p.Arg472Ter (c.1414C>T) is rare (popmax 0.585%, afr) (gnomAD).

BCO2 p.Arg472Ter

c.1414C>T · rs144345630 · VCV778561

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.585%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 10 of 12
REVEL	0.039	moderately benign-leaning
Splicing
SpliceAI	Δ0.28	donor loss, 16 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 1.7	GERP -0.039, phastCons 0.37
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.585% African / African-American · 439/75,032 alleles

Filtering AF 0.54% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.522%

Overall 0.0382% 617/1,613,934 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.585%	171
Middle Eastern	0.132%	758
Remaining individualsnot grpmax-eligible	0.0864%	1,158
Admixed American	0.0467%	2,143
East Asian	0.0111%	8,974
European (non-Finnish)	0.00661%	15,126
South Asian	0.00549%	18,213

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.Arg472Ter
Coding: c.1414C>T
MANE Select: NM_031938
dbSNP: rs144345630
Type: single nucleotide variant
Location: chr11:112214843 (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.Arg472Gln Likely benign ★ same residue
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-arg472ter (accessed [today's date]).

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