Is BBOF1 p.Ile503Thr (c.1508T>C) pathogenic?

BBOF1 p.Ile503Thr (c.1508T>C) is classified Uncertain significance in BBOF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-25). AlphaMissense: likely benign (0.0803); Very rare (popmax 0.00799%, afr).

How common is BBOF1 p.Ile503Thr (c.1508T>C) in the general population?

BBOF1 p.Ile503Thr (c.1508T>C) is very rare (popmax 0.00799%, afr) (gnomAD).

What do computational predictors say about BBOF1 p.Ile503Thr (c.1508T>C)?

AlphaMissense predicts likely benign (score 0.0803) — an in-silico prediction, not a clinical call.

BBOF1 p.Ile503Thr

c.1508T>C · VCV4645304

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0803 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00799%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0803	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -5.08	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.19	GERP -1.3, phastCons 0.033
Regional constraint	o/e 0.89	unconstrained · MANE · 45 kb · p 0.007 · regional, not allelic
Overall
CADD	9.571	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 0.00799% African / African-American · 6/75,050 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00228%

Overall 0.000992% 16/1,613,706 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00799%	12,508
East Asian	0.00446%	22,431
Remaining individualsnot grpmax-eligible	0.0032%	31,245
South Asian	0.0011%	91,046
European (non-Finnish)	0.000424%	235,938

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.Ile503Thr
Coding: c.1508T>C
MANE Select: NM_005589 · reported on NM_025057
Type: single nucleotide variant
Location: chr14:74057188 (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-ile503thr (accessed [today's date]).

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