Is BEAN1 p.Pro215His (c.644C>A) pathogenic?

BEAN1 p.Pro215His (c.644C>A) is classified Uncertain significance in BEAN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-22). AlphaMissense: likely benign (0.1676); Very rare (popmax 0.00411%, afr).

How common is BEAN1 p.Pro215His (c.644C>A) in the general population?

BEAN1 p.Pro215His (c.644C>A) is very rare (popmax 0.00411%, afr) (gnomAD).

What do computational predictors say about BEAN1 p.Pro215His (c.644C>A)?

AlphaMissense predicts likely benign (score 0.1676) — an in-silico prediction, not a clinical call.

BEAN1 p.Pro215His

c.644C>A · VCV4204665

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1676 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00411%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1676	likely benign
REVEL	0.168	moderately benign-leaning
SaProt	LLR -11.85	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	23.4	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 0.00411% African / African-American · 3/73,056 alleles

Filtering AF 0.00283% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00251%

Overall 0.00329% 51/1,550,066 alleles · very rare exomes 49/1,397,832 · genomes 2/152,234 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00411%	24,352
European (non-Finnish)	0.00375%	26,659
South Asian	0.00358%	27,965
Admixed American	0.00197%	50,884
Remaining individualsnot grpmax-eligible	0.00167%	60,042

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.Pro215His
Coding: c.644C>A
MANE Select: NM_001178020
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.Pro215Arg 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-pro215his (accessed [today's date]).

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