Is BAP1 p.Gly41Ser (c.121G>A) pathogenic?

BAP1 p.Gly41Ser (c.121G>A) is classified Benign/Likely benign in BAP1 (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.1449); Rare (popmax 0.433%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with BAP1 p.Gly41Ser (c.121G>A)?

BAP1 p.Gly41Ser (c.121G>A) is associated with hereditary neoplastic syndrome, BAP1-related tumor predisposition syndrome (ClinVar).

How common is BAP1 p.Gly41Ser (c.121G>A) in the general population?

BAP1 p.Gly41Ser (c.121G>A) is rare (popmax 0.433%, sas) (gnomAD).

What do computational predictors say about BAP1 p.Gly41Ser (c.121G>A)?

AlphaMissense predicts likely benign (score 0.1449) — an in-silico prediction, not a clinical call.

BAP1 p.Gly41Ser

c.121G>A · rs372586694 · VCV133667

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

AlphaMissense

likely benign

0.1449 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.433%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.1449	likely benign
REVEL	0.072	moderately benign-leaning
SaProt	LLR -6.49	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.30 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.6	GERP 1.4, phastCons 1
Overall
CADD	24.0	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 0.433% South Asian · 394/91,090 alleles

Filtering AF 0.397% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.383%

Overall 0.0368% 594/1,614,160 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.433%	231
Admixed American	0.0633%	1,580
Remaining individualsnot grpmax-eligible	0.0448%	2,232
Middle Eastern	0.033%	3,031
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,401
European (non-Finnish)	0.0103%	9,752
African / African-American	0.00933%	10,720

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.Gly41Ser
Coding: c.121G>A
MANE Select: NM_007212 · reported on NM_004656
dbSNP: rs372586694
Type: single nucleotide variant
Location: chr3:52409555 (GRCh38)
Structure: AlphaFold pLDDT 78.27 · 28 PDB
Residue 41: the 'interaction with hip2' region; a modified residue (phosphoserine)

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: BAP1-related tumor predisposition syndrome

Similar variants

BAP1 p.Gly41= Conflicting classifications of pathogenicity ★ same residue
BAP1 p.Gly41Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
BAP1 p.Gly41Arg Uncertain significance ★ ⚠ same residue
BAP1 p.Gly41Asp Uncertain significance ★ ⚠ same residue
BAP1 p.Gly41Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
BAP1 p.Gly41Val Uncertain significance ★ ⚠ same residue
BAP1 c.1117-1G>A Likely pathogenic ★★ same condition
BAP1 c.122+1G>A 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-gly41ser (accessed [today's date]).

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