Is BAP1 p.Gly41= (c.123C>T) pathogenic?

BAP1 p.Gly41= (c.123C>T) is classified Conflicting classifications of pathogenicity in BAP1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-07-21). Very rare (popmax 0.00111%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with BAP1 p.Gly41= (c.123C>T)?

BAP1 p.Gly41= (c.123C>T) is associated with hereditary neoplastic syndrome, BAP1-related tumor predisposition syndrome (ClinVar).

How common is BAP1 p.Gly41= (c.123C>T) in the general population?

BAP1 p.Gly41= (c.123C>T) is very rare (popmax 0.00111%, sas) (gnomAD).

BAP1 p.Gly41=

c.123C>T · rs2153228352 · VCV2876280

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00111%, sas)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP -0.48, phastCons 1
Overall
CADD	16.66	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00111% South Asian · 1/89,772 alleles

Overall 0.000137% 2/1,456,368 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00111%	89,772
European (non-Finnish)	8.49e-05%	1,177,722

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.Gly41=
Coding: c.123C>T
MANE Select: NM_007212 · reported on NM_004656
dbSNP: rs2153228352
Type: single nucleotide variant
Location: chr3:52408606 (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.Gly41Ser Benign/Likely benign ★★ 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-gly41 (accessed [today's date]).

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