Is BTBD1 p.Ala23Pro (c.67G>C) pathogenic?

BTBD1 p.Ala23Pro (c.67G>C) is classified Uncertain significance in BTBD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-06). AlphaMissense: likely benign (0.0648); Absent from gnomAD v4.1.

How common is BTBD1 p.Ala23Pro (c.67G>C) in the general population?

BTBD1 p.Ala23Pro (c.67G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BTBD1 p.Ala23Pro (c.67G>C)?

AlphaMissense predicts likely benign (score 0.0648) — an in-silico prediction, not a clinical call.

BTBD1 p.Ala23Pro

c.67G>C · rs2033295852 · VCV2389137

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0648 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0648	likely benign
REVEL	0.148	moderately benign-leaning
SaProt	LLR -5.42	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.17	GERP -2.6, phastCons 0.14
Regional constraint	o/e 1.06	unconstrained · MANE · 326 bp · p 0.48 · regional, not allelic
Overall
CADD	11.56	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

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: BTBD1
Protein: p.Ala23Pro
Coding: c.67G>C
MANE Select: NM_025238
dbSNP: rs2033295852
Type: single nucleotide variant
Location: chr15:83067085 (GRCh38)
Gene constraint: LOEUF 1.105 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.99
Residue 23: the 'disordered' region

Full BTBD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BTBD1 p.Ala162Gly Uncertain significance ★ ⚠ same type
BTBD1 p.Ala162Val Uncertain significance ★ ⚠ same type
BTBD1 p.Ala16Gly Uncertain significance ★ ⚠ same type
BTBD1 p.Ala82Val Uncertain significance ★ ⚠ same type
BTBD1 p.Ala84Val Uncertain significance ★ ⚠ same type
BTBD1 p.Ala8Thr Uncertain significance ★ ⚠ same type
BTBD1 p.Arg236Gln Uncertain significance ★ ⚠ same type
BTBD1 p.Arg236Gly 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/btbd1-p-ala23pro (accessed [today's date]).

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