Is BTC p.Val86Ala (c.257T>C) pathogenic?

BTC p.Val86Ala (c.257T>C) is classified Uncertain significance in BTC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-18). AlphaMissense: likely benign (0.1164); Absent from gnomAD v4.1.

How common is BTC p.Val86Ala (c.257T>C) in the general population?

BTC p.Val86Ala (c.257T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BTC p.Val86Ala (c.257T>C)?

AlphaMissense predicts likely benign (score 0.1164) — an in-silico prediction, not a clinical call.

BTC p.Val86Ala

c.257T>C · VCV4216762

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1164 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1164	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -6.78	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 3.8	GERP 0.62, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 46 kb · p 0.13 · regional, not allelic
Overall
CADD	19.53	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: BTC
Protein: p.Val86Ala
Coding: c.257T>C
MANE Select: NM_001729
Type: single nucleotide variant
Location: chr4:74755883 (GRCh38)
Gene constraint: LOEUF 1.209 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.51 · 4 PDB
Residue 86: a disulfide bond; a turn; the egf-like domain

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

Similar variants

BTC p.Leu44Phe Benign ★★ same type
BTC p.Ala5Val Uncertain significance ★ ⚠ same type
BTC p.Arg106Lys Uncertain significance ★ ⚠ same type
BTC p.Arg146Trp Uncertain significance ★ ⚠ same type
BTC p.Arg148Cys Uncertain significance ★ ⚠ same type
BTC p.Arg37Ile Uncertain significance ★ ⚠ same type
BTC p.Arg6Gly Uncertain significance ★ ⚠ same type
BTC p.Arg6Trp 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/btc-p-val86ala (accessed [today's date]).

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