Is BBOF1 p.Ser509Phe (c.1526C>T) pathogenic?

BBOF1 p.Ser509Phe (c.1526C>T) is classified Uncertain significance in BBOF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-02). AlphaMissense: likely benign (0.1124); Very rare (popmax 0.000339%, nfe).

How common is BBOF1 p.Ser509Phe (c.1526C>T) in the general population?

BBOF1 p.Ser509Phe (c.1526C>T) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about BBOF1 p.Ser509Phe (c.1526C>T)?

AlphaMissense predicts likely benign (score 0.1124) — an in-silico prediction, not a clinical call.

BBOF1 p.Ser509Phe

c.1526C>T · VCV4645303

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1124 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.1124	likely benign
REVEL	0.035	moderately benign-leaning
SaProt	LLR -8.07	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.6	GERP 1.1, phastCons 0.35
Regional constraint	o/e 0.89	unconstrained · MANE · 45 kb · p 0.007 · regional, not allelic
Overall
CADD	21.8	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 0.000339% European (non-Finnish) · 4/1,179,946 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,614,066 alleles · very rare exomes 4/1,461,756 · genomes 0/152,310 · joint denominator

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: BBOF1
Protein: p.Ser509Phe
Coding: c.1526C>T
MANE Select: NM_025057
Type: single nucleotide variant
Location: chr14:74057206 (GRCh38)

Full BBOF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/bbof1-p-ser509phe (accessed [today's date]).

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