Is BOLL p.Arg34Cys (c.100C>T) pathogenic?

BOLL p.Arg34Cys (c.100C>T) is classified Uncertain significance in BOLL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-12). AlphaMissense: likely pathogenic (0.9761); Very rare (popmax 0.00895%, eas).

How common is BOLL p.Arg34Cys (c.100C>T) in the general population?

BOLL p.Arg34Cys (c.100C>T) is very rare (popmax 0.00895%, eas) (gnomAD).

What do computational predictors say about BOLL p.Arg34Cys (c.100C>T)?

AlphaMissense predicts likely pathogenic (score 0.9761) — an in-silico prediction, not a clinical call.

BOLL p.Arg34Cys

c.100C>T · VCV3992387

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9761 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00895%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9761	likely pathogenic
REVEL	0.813	moderately pathogenic-leaning
SaProt	LLR -13.37	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.35	donor loss, 29 bp away · masked 0 · deltas
Pangolin	Δ0.25	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 53 kb · p 0.0053 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00895% East Asian · 4/44,688 alleles

Filtering AF 0.00299% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00181%

Overall 0.00139% 22/1,580,268 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00895%	11,172
Remaining individualsnot grpmax-eligible	0.0033%	30,332
African / African-American	0.00134%	74,594
European (non-Finnish)	0.0013%	77,190

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.Arg34Cys
Coding: c.100C>T
MANE Select: NM_033030
Type: single nucleotide variant
Location: chr2:197781751 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI 0.31 (gnomAD)
Structure: AlphaFold pLDDT 64.18
Residue 34: 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.Asp85Gly Uncertain significance ★ ⚠ same type
BOLL p.Cys165Gly Uncertain significance ★ ⚠ same type
BOLL p.Gln271His 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-arg34cys (accessed [today's date]).

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