Is BCO1 p.Arg161Cys (c.481C>T) pathogenic?

BCO1 p.Arg161Cys (c.481C>T) is classified Likely benign in BCO1 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-11-21). AlphaMissense: likely benign (0.1258); Rare (popmax 0.207%, nfe).

How common is BCO1 p.Arg161Cys (c.481C>T) in the general population?

BCO1 p.Arg161Cys (c.481C>T) is rare (popmax 0.207%, nfe) (gnomAD).

What do computational predictors say about BCO1 p.Arg161Cys (c.481C>T)?

AlphaMissense predicts likely benign (score 0.1258) — an in-silico prediction, not a clinical call.

BCO1 p.Arg161Cys

c.481C>T · rs147813781 · VCV3034681

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1258 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.207%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1258	likely benign
REVEL	0.508	indeterminate
SaProt	LLR -8.56	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.28	acceptor loss, 9 bp away · masked 0 · deltas
Pangolin	Δ0.27	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 3.2	GERP 0.038, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 52 kb · p 2.8e-05 · regional, not allelic
Overall
CADD	24.4	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 0.207% European (non-Finnish) · 2,443/1,179,920 alleles

Filtering AF 0.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.197%

Overall 0.177% 2,858/1,614,026 alleles · rare exomes 2,666/1,461,758 · genomes 192/152,268 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.23%	434
European (non-Finnish)grpmax	0.207%	483
Admixed American	0.172%	583
Middle Eastern	0.165%	606
South Asian	0.0955%	1,047
Finnishnot grpmax-eligible	0.0625%	1,601
African / African-American	0.0293%	3,410
Ashkenazi Jewishnot grpmax-eligible	0.0236%	4,229
East Asian	0.00446%	22,440

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg161Cys
Coding: c.481C>T
MANE Select: NM_017429
dbSNP: rs147813781
Type: single nucleotide variant
Location: chr16:81264649 (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.Arg161His Uncertain significance ★ ⚠ same residue
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

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-arg161cys (accessed [today's date]).

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