Is BEAN1 p.Arg86Trp (c.256C>T) pathogenic?

BEAN1 p.Arg86Trp (c.256C>T) is classified Uncertain significance in BEAN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-25). AlphaMissense: likely benign (0.1316); Very rare (popmax 0.0057%, nfe).

How common is BEAN1 p.Arg86Trp (c.256C>T) in the general population?

BEAN1 p.Arg86Trp (c.256C>T) is very rare (popmax 0.0057%, nfe) (gnomAD).

What do computational predictors say about BEAN1 p.Arg86Trp (c.256C>T)?

AlphaMissense predicts likely benign (score 0.1316) — an in-silico prediction, not a clinical call.

BEAN1 p.Arg86Trp

c.256C>T · VCV4204644

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1316 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0057%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1316	likely benign
REVEL	0.068	moderately benign-leaning
SaProt	LLR -10.04	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -0.97, phastCons 0.001
Regional constraint	o/e 0.96	unconstrained · MANE · 43 kb · p 0.44 · regional, not allelic
Overall
CADD	19.14	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 0.0057% European (non-Finnish) · 65/1,139,790 alleles

Filtering AF 0.00458% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00418%

Overall 0.0046% 70/1,520,212 alleles · very rare exomes 70/1,378,544 · genomes 0/141,668 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0057%	17,535
Remaining individualsnot grpmax-eligible	0.00336%	29,772
African / African-American	0.00288%	34,666
South Asian	0.00121%	82,852

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: BEAN1
Protein: p.Arg86Trp
Coding: c.256C>T
MANE Select: NM_001178020
Type: single nucleotide variant
Location: chr16:66469832 (GRCh38)
Gene constraint: LOEUF 1.45 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.44
Residue 86: the 'disordered' region

Full BEAN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BEAN1 p.Arg86Gln Uncertain significance ★ ⚠ same residue
BEAN1 p.Ala156Ser Uncertain significance ★★ ⚠ same type
BEAN1 p.Arg90Gln Uncertain significance ★★ ⚠ same type
BEAN1 p.Arg108His Likely benign ★★ same type
BEAN1 p.Arg76Ser Benign/Likely benign ★★ same type
BEAN1 p.Pro167= Likely benign ★★ same type
BEAN1 p.Tyr216= Likely benign ★★ same type
BEAN1 p.Tyr96= Likely 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/bean1-p-arg86trp (accessed [today's date]).

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