Is BOLL p.Ser280Arg (c.840C>A) pathogenic?

BOLL p.Ser280Arg (c.840C>A) is classified Uncertain significance in BOLL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-27). AlphaMissense: likely pathogenic (0.7628); Absent from gnomAD v4.1.

How common is BOLL p.Ser280Arg (c.840C>A) in the general population?

BOLL p.Ser280Arg (c.840C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BOLL p.Ser280Arg (c.840C>A)?

AlphaMissense predicts likely pathogenic (score 0.7628) — an in-silico prediction, not a clinical call.

BOLL p.Ser280Arg

c.840C>A · VCV4646387

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7628 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7628	likely pathogenic
REVEL	0.261	benign-leaning
SaProt	LLR -6.58	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.5	GERP 1.9, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 53 kb · p 0.0053 · regional, not allelic
Overall
CADD	20.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BOLL
Protein: p.Ser280Arg
Coding: c.840C>A
MANE Select: NM_033030
Type: single nucleotide variant
Location: chr2:197728567 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI 0.31 (gnomAD)
Structure: AlphaFold pLDDT 64.18

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-ser280arg (accessed [today's date]).

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