Is BCO1 p.Arg502Cys (c.1504C>T) pathogenic?

BCO1 p.Arg502Cys (c.1504C>T) is classified Uncertain significance in BCO1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-24). AlphaMissense: ambiguous (0.3646); Ultra-rare (popmax 0.0351%, sas).

How common is BCO1 p.Arg502Cys (c.1504C>T) in the general population?

BCO1 p.Arg502Cys (c.1504C>T) is ultra-rare (popmax 0.0351%, sas) (gnomAD).

What do computational predictors say about BCO1 p.Arg502Cys (c.1504C>T)?

AlphaMissense predicts ambiguous (score 0.3646) — an in-silico prediction, not a clinical call.

BCO1 p.Arg502Cys

c.1504C>T · rs772011367 · VCV2515068

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3646 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0351%, sas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3646	ambiguous
REVEL	0.857	moderately pathogenic-leaning
SaProt	LLR -14.79	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.5, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 52 kb · p 2.8e-05 · regional, not allelic
Overall
CADD	29.0	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 0.0351% South Asian · 32/91,084 alleles

Filtering AF 0.0256% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0222%

Overall 0.00242% 39/1,614,134 alleles · ultra-rare exomes 37/1,461,882 · genomes 2/152,252 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0351%	2,846
Remaining individualsnot grpmax-eligible	0.0016%	62,510
African / African-American	0.00133%	75,018
European (non-Finnish)	0.000424%	236,005

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.Arg502Cys
Coding: c.1504C>T
MANE Select: NM_017429
dbSNP: rs772011367
Type: single nucleotide variant
Location: chr16:81290437 (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

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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
BCO1 c.194-74A>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-arg502cys (accessed [today's date]).

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