Is BTBD6 p.Pro183Ser (c.547C>T) pathogenic?

BTBD6 p.Pro183Ser (c.547C>T) is classified Uncertain significance in BTBD6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-31). AlphaMissense: likely pathogenic (0.9555); Very rare (popmax 0.000169%, nfe).

How common is BTBD6 p.Pro183Ser (c.547C>T) in the general population?

BTBD6 p.Pro183Ser (c.547C>T) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about BTBD6 p.Pro183Ser (c.547C>T)?

AlphaMissense predicts likely pathogenic (score 0.9555) — an in-silico prediction, not a clinical call.

BTBD6 p.Pro183Ser

c.547C>T · rs771279024 · VCV2480002

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9555 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Computational evidence

Protein change
AlphaMissense	0.9555	likely pathogenic
REVEL	0.5	indeterminate
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 6	GERP 2.2, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 1,957 bp · p 0.9 · regional, not allelic
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P130S vs ClinVar P183S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,022 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,318 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: BTBD6
Protein: p.Pro183Ser
Coding: c.547C>T
MANE Select: NM_001519 · reported on NM_001387567
dbSNP: rs771279024
Type: single nucleotide variant
Location: chr14:105249441 (GRCh38)

Full BTBD6 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/btbd6-p-pro183ser (accessed [today's date]).

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