Is BACH2 p.Ser815Arg (c.2445C>A) pathogenic?

BACH2 p.Ser815Arg (c.2445C>A) is classified Uncertain significance in BACH2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-13). AlphaMissense: likely benign (0.3019); Very rare (popmax 0.00333%, amr).

How common is BACH2 p.Ser815Arg (c.2445C>A) in the general population?

BACH2 p.Ser815Arg (c.2445C>A) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about BACH2 p.Ser815Arg (c.2445C>A)?

AlphaMissense predicts likely benign (score 0.3019) — an in-silico prediction, not a clinical call.

BACH2 p.Ser815Arg

c.2445C>A · VCV3610199

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3019 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3019	likely benign
REVEL	0.11	moderately benign-leaning
SaProt	LLR -6.69	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 0.95	unconstrained · MANE · 320 bp · p 0.52 · regional, not allelic
Overall
CADD	24.1	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

Grpmax group 0.00333% Admixed American · 2/59,996 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000124% 2/1,613,942 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: BACH2
Protein: p.Ser815Arg
Coding: c.2445C>A
MANE Select: NM_021813
Type: single nucleotide variant
Location: chr6:89932489 (GRCh38)
Gene constraint: LOEUF 0.164 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.66 · 2 PDB
Residue 815: the 'disordered' region

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

Similar variants

BACH2 p.Ser815= Likely benign ★ same residue
BACH2 p.Ala148Val Uncertain significance ★★ ⚠ same type
BACH2 p.Ala205Thr Uncertain significance ★★ ⚠ same type
BACH2 p.Ala304Glu Uncertain significance ★★ ⚠ same type
BACH2 p.Ala479Val Uncertain significance ★★ ⚠ same type
BACH2 p.Ala529Val Uncertain significance ★★ ⚠ same type
BACH2 p.Ala747Val Uncertain significance ★★ ⚠ same type
BACH2 p.Ala756Val 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/bach2-p-ser815arg (accessed [today's date]).

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