Is BACH2 p.Ala418Val (c.1253C>T) pathogenic?

BACH2 p.Ala418Val (c.1253C>T) is classified Uncertain significance in BACH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). AlphaMissense: likely benign (0.0708); Absent from gnomAD v4.1; Associated with immunodeficiency 60.

What condition is associated with BACH2 p.Ala418Val (c.1253C>T)?

BACH2 p.Ala418Val (c.1253C>T) is associated with immunodeficiency 60 (ClinVar).

How common is BACH2 p.Ala418Val (c.1253C>T) in the general population?

BACH2 p.Ala418Val (c.1253C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BACH2 p.Ala418Val (c.1253C>T)?

AlphaMissense predicts likely benign (score 0.0708) — an in-silico prediction, not a clinical call.

BACH2 p.Ala418Val

c.1253C>T · VCV4278036

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0708 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

immunodeficiency 60

Computational evidence

Protein change
AlphaMissense	0.0708	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -6.25	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 8.7	GERP 1.5, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 534 bp · p 0.87 · regional, not allelic
Overall
CADD	20.9	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: BACH2
Protein: p.Ala418Val
Coding: c.1253C>T
MANE Select: NM_021813
Type: single nucleotide variant
Location: chr6:89950853 (GRCh38)
Gene constraint: LOEUF 0.164 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.66 · 2 PDB
Residue 418: a UniProt-annotated variant site (in)

Full BACH2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

immunodeficiency 60 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BACH2 p.Ala418Thr Benign ★★ same residue
BACH2 p.Ala418Ser Uncertain significance ★ ⚠ same residue
BACH2 p.Ala148Val Uncertain significance ★★ ⚠ same condition
BACH2 p.Ala756Val Uncertain significance ★★ ⚠ same condition
BACH2 p.Asp34Asn Uncertain significance ★★ ⚠ same condition
BACH2 p.Gln378His Uncertain significance ★★ ⚠ same condition
BACH2 p.Gln578Lys Uncertain significance ★★ ⚠ same condition
BACH2 p.Glu788Lys Uncertain significance ★★ ⚠ same condition

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/bach2-p-ala418val (accessed [today's date]).

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