Is BTBD16 p.Pro96Ser (c.286C>T) pathogenic?

BTBD16 p.Pro96Ser (c.286C>T) is classified Uncertain significance in BTBD16 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-01). AlphaMissense: likely benign (0.1877); Absent from gnomAD v4.1.

How common is BTBD16 p.Pro96Ser (c.286C>T) in the general population?

BTBD16 p.Pro96Ser (c.286C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BTBD16 p.Pro96Ser (c.286C>T)?

AlphaMissense predicts likely benign (score 0.1877) — an in-silico prediction, not a clinical call.

BTBD16 p.Pro96Ser

c.286C>T · VCV4216658

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1877 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1877	likely benign
REVEL	0.068	moderately benign-leaning
SaProt	LLR -3.97	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 0.72	GERP -2.4, phastCons 0.16
Regional constraint	o/e 1.03	unconstrained · MANE · 63 kb · p 0.47 · regional, not allelic
Overall
CADD	14.87	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: BTBD16
Protein: p.Pro96Ser
Coding: c.286C>T
MANE Select: NM_144587
Type: single nucleotide variant
Location: chr10:122286149 (GRCh38)
Gene constraint: LOEUF 1.246 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.92

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-pro96ser (accessed [today's date]).

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