Is BOLL p.Lys73Arg (c.218A>G) pathogenic?

BOLL p.Lys73Arg (c.218A>G) is classified Uncertain significance in BOLL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-02). AlphaMissense: ambiguous (0.515); Very rare (popmax 0.00936%, afr).

How common is BOLL p.Lys73Arg (c.218A>G) in the general population?

BOLL p.Lys73Arg (c.218A>G) is very rare (popmax 0.00936%, afr) (gnomAD).

What do computational predictors say about BOLL p.Lys73Arg (c.218A>G)?

AlphaMissense predicts ambiguous (score 0.515) — an in-silico prediction, not a clinical call.

BOLL p.Lys73Arg

c.218A>G · VCV3481555

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.515 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00936%, afr)

Computational evidence

Protein change
AlphaMissense	0.515	ambiguous
REVEL	0.307	indeterminate
SaProt	LLR -10.02	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 0.64, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 53 kb · p 0.0053 · regional, not allelic
Overall
CADD	24.8	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 0.00936% African / African-American · 7/74,820 alleles

Filtering AF 0.00438% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.000497% 8/1,608,256 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00936%	10,689
Remaining individualsnot grpmax-eligible	0.00161%	62,274

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: BOLL
Protein: p.Lys73Arg
Coding: c.218A>G
MANE Select: NM_033030
Type: single nucleotide variant
Location: chr2:197778978 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI 0.31 (gnomAD)
Structure: AlphaFold pLDDT 64.18
Residue 73: the rrm domain

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

Similar variants

BOLL p.Ala172Pro Uncertain significance ★ ⚠ same type
BOLL p.Ala172Val Uncertain significance ★ ⚠ same type
BOLL p.Ala185Asp Uncertain significance ★ ⚠ same type
BOLL p.Ala259Asp Uncertain significance ★ ⚠ same type
BOLL p.Ala267Val Uncertain significance ★ ⚠ same type
BOLL p.Arg34Cys Uncertain significance ★ ⚠ same type
BOLL p.Asp85Gly Uncertain significance ★ ⚠ same type
BOLL p.Cys165Gly Uncertain significance ★ ⚠ same type

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/boll-p-lys73arg (accessed [today's date]).

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