Is BAP1 p.Gly470Arg (c.1408G>A) pathogenic?

BAP1 p.Gly470Arg (c.1408G>A) is classified Conflicting classifications of pathogenicity in BAP1 (ClinVar, Conflicting submitters, 12 submitters; last evaluated 2026-01-28). AlphaMissense: ambiguous (0.5054); Ultra-rare (popmax 0.0483%, amr); Associated with Hereditary cancer.

What condition is associated with BAP1 p.Gly470Arg (c.1408G>A)?

BAP1 p.Gly470Arg (c.1408G>A) is associated with Hereditary cancer, BAP1-related tumor predisposition syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BAP1 p.Gly470Arg (c.1408G>A) in the general population?

BAP1 p.Gly470Arg (c.1408G>A) is ultra-rare (popmax 0.0483%, amr) (gnomAD).

What do computational predictors say about BAP1 p.Gly470Arg (c.1408G>A)?

AlphaMissense predicts ambiguous (score 0.5054) — an in-silico prediction, not a clinical call.

BAP1 p.Gly470Arg

c.1408G>A · rs576538858 · VCV133663

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 12 submitters

AlphaMissense

ambiguous

0.5054 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0483%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Hereditary cancer

Computational evidence

Protein change
AlphaMissense	0.5054	ambiguous
REVEL	0.117	moderately benign-leaning
SaProt	LLR -4.91	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2.1, phastCons 1
Overall
CADD	20.7	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 0.0483% Admixed American · 29/60,022 alleles

Filtering AF 0.0345% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0299%

Overall 0.00415% 67/1,614,024 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0483%	2,070
Remaining individualsnot grpmax-eligible	0.0144%	6,945
European (non-Finnish)	0.0022%	45,385
South Asian	0.0022%	45,544
African / African-American	0.00133%	75,012

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: BAP1
Protein: p.Gly470Arg
Coding: c.1408G>A
MANE Select: NM_007212 · reported on NM_004656
dbSNP: rs576538858
Type: single nucleotide variant
Location: chr3:52403737 (GRCh38)
Structure: AlphaFold pLDDT 78.27 · 28 PDB

Full BAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Hereditary cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: BAP1-related tumor predisposition syndrome hereditary neoplastic syndrome

Similar variants

BAP1 p.Gly470= Benign/Likely benign ★★ same residue
BAP1 p.Gly470Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
BAP1 c.1117-1G>A Likely pathogenic ★★ same condition
BAP1 c.122+1G>A Pathogenic ★★ same condition
BAP1 c.122+1G>T Pathogenic/Likely pathogenic ★★ same condition
BAP1 c.122+5G>A Pathogenic/Likely pathogenic ★★ same condition
BAP1 c.122+5G>C Likely pathogenic ★★ same condition
BAP1 c.1251-1G>A Likely pathogenic ★★ same condition

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/bap1-p-gly470arg (accessed [today's date]).

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