Is BACH1 p.Ser314Pro (c.940T>C) pathogenic?

BACH1 p.Ser314Pro (c.940T>C) is classified Benign in BACH1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-18). AlphaMissense: likely benign (0.0771); Common (popmax 7.79%, afr) — too common for a highly-penetrant pathogenic allele; Associated with BACH1-related disorder.

What condition is associated with BACH1 p.Ser314Pro (c.940T>C)?

BACH1 p.Ser314Pro (c.940T>C) is associated with BACH1-related disorder (ClinVar).

What do computational predictors say about BACH1 p.Ser314Pro (c.940T>C)?

AlphaMissense predicts likely benign (score 0.0771) — an in-silico prediction, not a clinical call.

BACH1 p.Ser314Pro

Q: How common is BACH1 p.Ser314Pro (c.940T>C) in the general population?

BACH1 p.Ser314Pro (c.940T>C) is common (popmax 7.79%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.940T>C · rs35474725 · VCV3055804

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0771 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 7.79%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

BACH1-related disorder

Computational evidence

Protein change
AlphaMissense	0.0771	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -7.14	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 -0.003	GERP -0.95, phastCons 0.001
Regional constraint	o/e 0.93	unconstrained · MANE · 22 kb · p 0.029 · regional, not allelic
Overall
CADD	13.17	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

Grpmax group 7.79% African / African-American · 5,844/75,024 alleles

Filtering AF 7.62% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.55%

Overall 0.413% 6,666/1,614,012 alleles · common exomes 3,209/1,461,702 · genomes 3,457/152,310 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.79%	13
Remaining individualsnot grpmax-eligible	0.578%	173
Admixed American	0.515%	194
Middle Eastern	0.264%	379
South Asian	0.011%	9,109
European (non-Finnish)	0.0107%	9,365

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: BACH1
Protein: p.Ser314Pro
Coding: c.940T>C
MANE Select: NM_001186
dbSNP: rs35474725
Type: single nucleotide variant
Location: chr21:29326764 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.17 · 12 PDB
Residue 314: a UniProt-annotated variant site (in)

Full BACH1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

BACH1-related disorder

Similar variants

BACH1 p.Glu363Gln Uncertain significance ⚠ same condition
BACH1 p.Asp280= Likely benign same condition
BACH1 p.Cys270Gly Likely benign same condition
BACH1 p.Gly611= Benign same condition
BACH1 p.Ile498Phe Benign same condition
BACH1 p.Ala193Gly Uncertain significance ★ ⚠ same type
BACH1 p.Ala203Thr Uncertain significance ★ ⚠ same type
BACH1 p.Ala233Gly 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/bach1-p-ser314pro (accessed [today's date]).

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