Is BEAN1 p.Arg76Ser (c.226C>A) pathogenic?

BEAN1 p.Arg76Ser (c.226C>A) is classified Benign/Likely benign in BEAN1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-01). AlphaMissense: likely benign (0.229); Low-frequency (popmax 1.13%, nfe).

How common is BEAN1 p.Arg76Ser (c.226C>A) in the general population?

BEAN1 p.Arg76Ser (c.226C>A) is low-frequency (popmax 1.13%, nfe) (gnomAD).

What do computational predictors say about BEAN1 p.Arg76Ser (c.226C>A)?

AlphaMissense predicts likely benign (score 0.229) — an in-silico prediction, not a clinical call.

BEAN1 p.Arg76Ser

c.226C>A · rs200706119 · VCV2646598

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.229 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.13%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.229	likely benign
REVEL	0.063	moderately benign-leaning
SaProt	LLR -8.14	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.4	GERP 0.13, phastCons 0.72
Regional constraint	o/e 0.96	unconstrained · MANE · 43 kb · p 0.44 · regional, not allelic
Overall
CADD	16.84	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 1.13% European (non-Finnish) · 12,916/1,146,824 alleles

Filtering AF 1.11% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1%

Overall 1.01% 15,450/1,535,802 alleles · low-frequency exomes 14,219/1,383,682 · genomes 1,231/152,120 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	2.37%	42
Amishnot grpmax-eligible	1.75%	57
European (non-Finnish)grpmax	1.13%	89
South Asian	0.79%	127
Remaining individualsnot grpmax-eligible	0.753%	133
Middle Eastern	0.625%	160
Admixed American	0.337%	297
African / African-American	0.144%	696
Ashkenazi Jewishnot grpmax-eligible	0.112%	895
East Asian	0.00245%	40,894

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: BEAN1
Protein: p.Arg76Ser
Coding: c.226C>A
MANE Select: NM_001178020
dbSNP: rs200706119
Type: single nucleotide variant
Location: chr16:66469802 (GRCh38)
Gene constraint: LOEUF 1.45 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.44
Residue 76: 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.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
BEAN1 p.Ala165Thr 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-arg76ser (accessed [today's date]).

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