Is BTBD16 p.Ile150Phe (c.448A>T) pathogenic?

BTBD16 p.Ile150Phe (c.448A>T) is classified Uncertain significance in BTBD16 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-11). AlphaMissense: ambiguous (0.4191); Very rare (popmax 8.48e-05%, nfe).

How common is BTBD16 p.Ile150Phe (c.448A>T) in the general population?

BTBD16 p.Ile150Phe (c.448A>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about BTBD16 p.Ile150Phe (c.448A>T)?

AlphaMissense predicts ambiguous (score 0.4191) — an in-silico prediction, not a clinical call.

BTBD16 p.Ile150Phe

c.448A>T · VCV3482731

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4191 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4191	ambiguous
REVEL	0.424	indeterminate
SaProt	LLR -7.28	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP 0.98, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 63 kb · p 0.47 · regional, not allelic
Overall
CADD	23.6	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 8.48e-05% European (non-Finnish) · 1/1,179,732 alleles

Overall 6.84e-05% 1/1,461,486 alleles · very rare

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: BTBD16
Protein: p.Ile150Phe
Coding: c.448A>T
MANE Select: NM_144587
Type: single nucleotide variant
Location: chr10:122289971 (GRCh38)
Gene constraint: LOEUF 1.246 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.92
Residue 150: the btb domain

Full BTBD16 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BTBD16 p.Ala113Val Uncertain significance ★ ⚠ same type
BTBD16 p.Ala161Thr Uncertain significance ★ ⚠ same type
BTBD16 p.Ala204Asp Uncertain significance ★ ⚠ same type
BTBD16 p.Ala362Thr Uncertain significance ★ ⚠ same type
BTBD16 p.Ala505Val Uncertain significance ★ ⚠ same type
BTBD16 p.Arg13Cys Uncertain significance ★ ⚠ same type
BTBD16 p.Arg197Ser Uncertain significance ★ ⚠ same type
BTBD16 p.Arg21Trp 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/btbd16-p-ile150phe (accessed [today's date]).

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