Is BOLA3 p.Arg99= (c.297G>A) pathogenic?

BOLA3 p.Arg99= (c.297G>A) is classified Likely benign in BOLA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-22). Very rare (popmax 0.00254%, nfe); Associated with Inborn genetic diseases.

What condition is associated with BOLA3 p.Arg99= (c.297G>A)?

BOLA3 p.Arg99= (c.297G>A) is associated with Inborn genetic diseases (ClinVar).

How common is BOLA3 p.Arg99= (c.297G>A) in the general population?

BOLA3 p.Arg99= (c.297G>A) is very rare (popmax 0.00254%, nfe) (gnomAD).

BOLA3 p.Arg99=

c.297G>A · VCV4214805

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00254%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.043	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.52	GERP -0.52, phastCons 1
Overall
CADD	15.96	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00254% European (non-Finnish) · 30/1,179,992 alleles

Filtering AF 0.0018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00156%

Overall 0.00212% 31/1,461,826 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00254%	39,333
South Asian	0.0011%	91,068

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: BOLA3
Protein: p.Arg99=
Coding: c.297G>A
MANE Select: NM_212552
Type: single nucleotide variant
Location: chr2:74135620 (GRCh38)
Gene constraint: LOEUF 1.712 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.33 · 1 PDB
Residue 99: a β-strand; a UniProt-annotated variant site (in mmds2)

Full BOLA3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BOLA3 p.Arg99Gln Uncertain significance ★★ ⚠ same residue
BOLA3 p.Arg99Leu Uncertain significance ★ ⚠ same residue
BOLA3 p.Arg99Trp Uncertain significance ★ ⚠ same residue
BOLA3 p.Arg107His Uncertain significance ★★ ⚠ same condition
BOLA3 p.Arg24Gln Uncertain significance ★★ ⚠ same condition
BOLA3 p.Gln86Glu Uncertain significance ★★ ⚠ same condition
BOLA3 p.Ile100Val Uncertain significance ★★ ⚠ same condition
BOLA3 p.Ile55Thr Uncertain significance ★★ ⚠ 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/bola3-p-arg99 (accessed [today's date]).

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