Is BEAN1 p.Val136Met (c.406G>A) pathogenic?

BEAN1 p.Val136Met (c.406G>A) is classified Uncertain significance in BEAN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-09). AlphaMissense: likely benign (0.1349); Ultra-rare (popmax 0.0147%, eas).

How common is BEAN1 p.Val136Met (c.406G>A) in the general population?

BEAN1 p.Val136Met (c.406G>A) is ultra-rare (popmax 0.0147%, eas) (gnomAD).

What do computational predictors say about BEAN1 p.Val136Met (c.406G>A)?

AlphaMissense predicts likely benign (score 0.1349) — an in-silico prediction, not a clinical call.

BEAN1 p.Val136Met

c.406G>A · VCV3480391

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1349 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1349	likely benign
REVEL	0.167	moderately benign-leaning
SaProt	LLR -7.97	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 3.9	GERP 0.46, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 43 kb · p 0.44 · regional, not allelic
Overall
CADD	20.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0147% East Asian · 6/40,774 alleles

Filtering AF 0.00637% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00436%

Overall 0.000451% 7/1,550,410 alleles · ultra-rare exomes 5/1,398,058 · genomes 2/152,352 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0147%	6,796
South Asian	0.00119%	83,830

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.Val136Met
Coding: c.406G>A
MANE Select: NM_001178020
Type: single nucleotide variant
Location: chr16:66477676 (GRCh38)
Gene constraint: LOEUF 1.45 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.44

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-val136met (accessed [today's date]).

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