Is BCO1 p.Cys541= (c.1623C>T) pathogenic?

BCO1 p.Cys541= (c.1623C>T) is classified Likely benign in BCO1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-11). Ultra-rare (popmax 0.0481%, afr).

How common is BCO1 p.Cys541= (c.1623C>T) in the general population?

BCO1 p.Cys541= (c.1623C>T) is ultra-rare (popmax 0.0481%, afr) (gnomAD).

BCO1 p.Cys541=

c.1623C>T · VCV4931485

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0481%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.2	GERP -3.8
Overall
CADD	0.324	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0481% African / African-American · 36/74,902 alleles

Filtering AF 0.0357% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0314%

Overall 0.0026% 42/1,613,504 alleles · ultra-rare exomes 18/1,461,364 · genomes 24/152,140 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0481%	2,081
Remaining individualsnot grpmax-eligible	0.008%	12,495
Admixed American	0.00167%	59,986

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.Cys541=
Coding: c.1623C>T
MANE Select: NM_017429
Type: single nucleotide variant
Location: chr16:81290556 (GRCh38)
Gene constraint: LOEUF 1.17 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.03
Residue 541: the 'disordered' region

Full BCO1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BCO1 p.Cys541Tyr Conflicting classifications of pathogenicity ★ ⚠ 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-cys541 (accessed [today's date]).

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