Is BAK1 p.Thr148Ile (c.443C>T) pathogenic?

BAK1 p.Thr148Ile (c.443C>T) is classified Uncertain significance in BAK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-05). AlphaMissense: likely benign (0.2513); Absent from gnomAD v4.1.

How common is BAK1 p.Thr148Ile (c.443C>T) in the general population?

BAK1 p.Thr148Ile (c.443C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BAK1 p.Thr148Ile (c.443C>T)?

AlphaMissense predicts likely benign (score 0.2513) — an in-silico prediction, not a clinical call.

BAK1 p.Thr148Ile

c.443C>T · VCV4193690

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2513 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2513	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -7.27	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.27	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 4.8	GERP -0.8, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 3,798 bp · p 3.2e-07 · regional, not allelic
Overall
CADD	22.3	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: BAK1
Protein: p.Thr148Ile
Coding: c.443C>T
MANE Select: NM_001188
Type: single nucleotide variant
Location: chr6:33574122 (GRCh38)
Gene constraint: LOEUF 1.197 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.82 · 55 PDB
Residue 148: a β-strand

Full BAK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BAK1 p.Thr148Asn Uncertain significance ★ ⚠ same residue
BAK1 p.Arg127Pro Uncertain significance ★ ⚠ same type
BAK1 p.Arg169Trp Uncertain significance ★ ⚠ same type
BAK1 p.Arg206Gln Uncertain significance ★ ⚠ same type
BAK1 p.Arg207Thr Uncertain significance ★ ⚠ same type
BAK1 p.Arg36His Uncertain significance ★ ⚠ same type
BAK1 p.Arg76Trp Uncertain significance ★ ⚠ same type
BAK1 p.Asn124Ile 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/bak1-p-thr148ile (accessed [today's date]).

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