Is BEAN1 p.Arg73Cys (c.217C>T) pathogenic?

BEAN1 p.Arg73Cys (c.217C>T) is classified Uncertain significance in BEAN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-12). AlphaMissense: likely benign (0.1661); Ultra-rare (popmax 0.0138%, amr).

How common is BEAN1 p.Arg73Cys (c.217C>T) in the general population?

BEAN1 p.Arg73Cys (c.217C>T) is ultra-rare (popmax 0.0138%, amr) (gnomAD).

What do computational predictors say about BEAN1 p.Arg73Cys (c.217C>T)?

AlphaMissense predicts likely benign (score 0.1661) — an in-silico prediction, not a clinical call.

BEAN1 p.Arg73Cys

c.217C>T · rs890742299 · VCV3133649

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1661 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0138%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1661	likely benign
REVEL	0.099	moderately benign-leaning
SaProt	LLR -10.07	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.7	GERP 0.37, phastCons 0.03
Regional constraint	o/e 0.96	unconstrained · MANE · 43 kb · p 0.44 · regional, not allelic
Overall
CADD	24.1	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 0.0138% Admixed American · 7/50,906 alleles

Filtering AF 0.00639% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00456%

Overall 0.00437% 67/1,534,304 alleles · ultra-rare exomes 58/1,382,900 · genomes 9/151,404 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0138%	7,272
Remaining individualsnot grpmax-eligible	0.00501%	19,973
European (non-Finnish)	0.00454%	22,048
African / African-American	0.00416%	24,053
Ashkenazi Jewishnot grpmax-eligible	0.0035%	28,598
South Asian	0.00119%	83,982

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.Arg73Cys
Coding: c.217C>T
MANE Select: NM_001178020
dbSNP: rs890742299
Type: single nucleotide variant
Location: chr16:66469793 (GRCh38)
Gene constraint: LOEUF 1.45 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.44
Residue 73: the 'disordered' region

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

Similar variants

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
BEAN1 p.Ala10Thr Uncertain significance ★ ⚠ 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-arg73cys (accessed [today's date]).

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