Is BTRC p.Trp286Arg (c.856T>C) pathogenic?

BTRC p.Trp286Arg (c.856T>C) is classified Uncertain significance in BTRC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-07). AlphaMissense: likely pathogenic (0.9999); Absent from gnomAD v4.1.

How common is BTRC p.Trp286Arg (c.856T>C) in the general population?

BTRC p.Trp286Arg (c.856T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BTRC p.Trp286Arg (c.856T>C)?

AlphaMissense predicts likely pathogenic (score 0.9999) — an in-silico prediction, not a clinical call.

BTRC p.Trp286Arg

c.856T>C · VCV4216910

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9999 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9999	likely pathogenic · top 10% in BTRC
REVEL	0.637	indeterminate
SaProt	LLR -12.60	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.6, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 29 kb · p 5.9e-09 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: BTRC
Protein: p.Trp286Arg
Coding: c.856T>C
MANE Select: NM_033637
Type: single nucleotide variant
Location: chr10:101532310 (GRCh38)
Gene constraint: LOEUF 0.643 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.33 · 15 PDB
Residue 286: an α-helix

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

Similar variants

BTRC p.Leu271Phe Uncertain significance ★★ ⚠ same type
BTRC p.Leu86Phe Uncertain significance ★★ ⚠ same type
BTRC c.556+7C>G Benign ★★ same type
BTRC p.Ala543Ser Benign ★★ same type
BTRC p.Ile229= Benign ★★ same type
BTRC p.Leu387= Likely benign ★★ same type
BTRC p.Pro592Arg Likely benign ★★ same type
BTRC p.Pro592His Benign ★★ 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/btrc-p-trp286arg (accessed [today's date]).

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