Is BCO1 p.Ala379Val (c.1136C>T) pathogenic?

BCO1 p.Ala379Val (c.1136C>T) is classified Benign in BCO1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2021-06-09). AlphaMissense: likely benign (0.0983); Common (popmax 23.7%, nfe) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about BCO1 p.Ala379Val (c.1136C>T)?

AlphaMissense predicts likely benign (score 0.0983) — an in-silico prediction, not a clinical call.

BCO1 p.Ala379Val

Q: How common is BCO1 p.Ala379Val (c.1136C>T) in the general population?

BCO1 p.Ala379Val (c.1136C>T) is common (popmax 23.7%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1136C>T · rs7501331 · VCV1253021

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0983 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 23.7%, nfe) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0983	likely benign
REVEL	0.209	benign-leaning
SaProt	LLR -7.68	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 1.3, phastCons 0.027
Regional constraint	o/e 1.16	unconstrained · MANE · 52 kb · p 2.8e-05 · regional, not allelic
Overall
CADD	18.16	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 23.7% European (non-Finnish) · 279,579/1,178,046 alleles

Filtering AF 23.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 23.6%

Overall 22.1% 356,666/1,611,860 alleles · common exomes 329,596/1,459,740 · genomes 27,070/152,120 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	32.2%	3
European (non-Finnish)grpmax	23.7%	4
Remaining individualsnot grpmax-eligible	21%	5
South Asian	19.5%	5
Admixed American	17.5%	6
Middle Eastern	16%	6
East Asian	15%	7
Ashkenazi Jewishnot grpmax-eligible	14.5%	7
Amishnot grpmax-eligible	14%	7
African / African-American	4.11%	24

Finnish 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.Ala379Val
Coding: c.1136C>T
MANE Select: NM_017429
dbSNP: rs7501331
Type: single nucleotide variant
Location: chr16:81280891 (GRCh38)
Gene constraint: LOEUF 1.17 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.03
Residue 379: a UniProt-annotated variant site (in)

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

Similar variants

BCO1 p.Ala379Ser Likely benign ★ 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-ala379val (accessed [today's date]).

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