Is BACH2 p.Asn765= (c.2295C>T) pathogenic?

BACH2 p.Asn765= (c.2295C>T) is classified Benign in BACH2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-04). Common (popmax 15.9%, mid) — too common for a highly-penetrant pathogenic allele.

BACH2 p.Asn765=

Q: How common is BACH2 p.Asn765= (c.2295C>T) in the general population?

BACH2 p.Asn765= (c.2295C>T) is common (popmax 15.9%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2295C>T · rs3798789 · VCV1166831

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 15.9%, mid) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.3	GERP -3
Overall
CADD	0.415	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 15.9% Middle Eastern · 963/6,048 alleles

Filtering AF 15.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 14.8%

Overall 10.9% 175,880/1,613,874 alleles · common

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	22.2%	4
Amishnot grpmax-eligible	16.8%	6
Middle Easterngrpmax	15.9%	6
Finnishnot grpmax-eligible	13.3%	8
African / African-American	13.3%	8
Remaining individualsnot grpmax-eligible	11.4%	9
European (non-Finnish)	10.8%	9
South Asian	9.54%	10
Admixed American	6.73%	15
East Asian	5.32%	19

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asn765=
Coding: c.2295C>T
MANE Select: NM_021813
dbSNP: rs3798789
Type: single nucleotide variant
Location: chr6:89932639 (GRCh38)
Gene constraint: LOEUF 0.164 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.66 · 2 PDB

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

Similar variants

BACH2 p.Asn765Ser Uncertain significance ★ ⚠ 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-asn765 (accessed [today's date]).

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