Is BEAN1 p.Pro215Arg (c.644C>G) pathogenic?

BEAN1 p.Pro215Arg (c.644C>G) is classified Uncertain significance in BEAN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-10). AlphaMissense: likely benign (0.1315); Ultra-rare (popmax 0.032%, nfe).

How common is BEAN1 p.Pro215Arg (c.644C>G) in the general population?

BEAN1 p.Pro215Arg (c.644C>G) is ultra-rare (popmax 0.032%, nfe) (gnomAD).

What do computational predictors say about BEAN1 p.Pro215Arg (c.644C>G)?

AlphaMissense predicts likely benign (score 0.1315) — an in-silico prediction, not a clinical call.

BEAN1 p.Pro215Arg

c.644C>G · rs533744789 · VCV2463240

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1315 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.032%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1315	likely benign
REVEL	0.241	benign-leaning
SaProt	LLR -10.36	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 4.4	GERP 1.8, phastCons 0.52
Regional constraint	o/e 0.96	unconstrained · MANE · 43 kb · p 0.44 · regional, not allelic
Overall
CADD	22.1	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 0.032% European (non-Finnish) · 367/1,146,356 alleles

Filtering AF 0.0293% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0282%

Overall 0.0263% 407/1,550,066 alleles · ultra-rare exomes 381/1,397,832 · genomes 26/152,234 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.032%	3,124
Remaining individualsnot grpmax-eligible	0.0233%	4,289
African / African-American	0.0192%	5,218
South Asian	0.00715%	13,983
Finnishnot grpmax-eligible	0.00673%	14,861
Admixed American	0.00393%	25,442

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.Pro215Arg
Coding: c.644C>G
MANE Select: NM_001178020
dbSNP: rs533744789
Type: single nucleotide variant
Location: chr16:66480789 (GRCh38)
Gene constraint: LOEUF 1.45 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.44
Residue 215: the 'disordered' region

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

Similar variants

BEAN1 p.Pro215His 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-pro215arg (accessed [today's date]).

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