Is BTC p.Ile136Val (c.406A>G) pathogenic?

BTC p.Ile136Val (c.406A>G) is classified Likely benign in BTC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-29). AlphaMissense: likely benign (0.0613); Absent from gnomAD v4.1.

How common is BTC p.Ile136Val (c.406A>G) in the general population?

BTC p.Ile136Val (c.406A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BTC p.Ile136Val (c.406A>G)?

AlphaMissense predicts likely benign (score 0.0613) — an in-silico prediction, not a clinical call.

BTC p.Ile136Val

c.406A>G · VCV3825966

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0613 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0613	likely benign
REVEL	0.007	strongly benign-leaning
SaProt	LLR -5.83	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 -1.5	GERP -4.6
Regional constraint	o/e 1.10	unconstrained · MANE · 46 kb · p 0.13 · regional, not allelic
Overall
CADD	0.049	PHRED · no single calibrated threshold — expert panels disagree

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.Ile136Val
Coding: c.406A>G
MANE Select: NM_001729
Type: single nucleotide variant
Location: chr4:74750595 (GRCh38)
Gene constraint: LOEUF 1.209 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.51 · 4 PDB

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-ile136val (accessed [today's date]).

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