Is BAP1 p.Arg383His (c.1148G>A) pathogenic?

BAP1 p.Arg383His (c.1148G>A) is classified Uncertain significance in BAP1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-13). AlphaMissense: likely benign (0.1432); Very rare (popmax 0.00533%, afr); Associated with melanoma, uveal, susceptibility to, 2.

What condition is associated with BAP1 p.Arg383His (c.1148G>A)?

BAP1 p.Arg383His (c.1148G>A) is associated with melanoma, uveal, susceptibility to, 2, BAP1-related tumor predisposition syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BAP1 p.Arg383His (c.1148G>A) in the general population?

BAP1 p.Arg383His (c.1148G>A) is very rare (popmax 0.00533%, afr) (gnomAD).

What do computational predictors say about BAP1 p.Arg383His (c.1148G>A)?

AlphaMissense predicts likely benign (score 0.1432) — an in-silico prediction, not a clinical call.

BAP1 p.Arg383His

c.1148G>A · rs374620220 · VCV412440

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1432 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00533%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

melanoma, uveal, susceptibility to, 2

Computational evidence

Protein change
AlphaMissense	0.1432	likely benign
REVEL	0.234	benign-leaning
SaProt	LLR -7.11	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1
Overall
CADD	29.0	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 0.00533% African / African-American · 4/75,034 alleles

Filtering AF 0.00174% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00089% 13/1,461,206 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00533%	18,758
East Asian	0.00223%	44,874
Remaining individualsnot grpmax-eligible	0.0016%	62,434
South Asian	0.0011%	91,026
European (non-Finnish)	0.000509%	196,652

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.Arg383His
Coding: c.1148G>A
MANE Select: NM_007212 · reported on NM_004656
dbSNP: rs374620220
Type: single nucleotide variant
Location: chr3:52404555 (GRCh38)
Structure: AlphaFold pLDDT 78.27 · 28 PDB

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

Disease context

melanoma, uveal, susceptibility to, 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

BAP1 p.Arg383= Benign/Likely benign ★★ same residue
BAP1 p.Arg383Cys 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-arg383his (accessed [today's date]).

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