Is BACH1 p.Thr508= (c.1524C>T) pathogenic?

BACH1 p.Thr508= (c.1524C>T) is classified Likely benign in BACH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-05). Ultra-rare (popmax 0.0176%, sas).

How common is BACH1 p.Thr508= (c.1524C>T) in the general population?

BACH1 p.Thr508= (c.1524C>T) is ultra-rare (popmax 0.0176%, sas) (gnomAD).

BACH1 p.Thr508=

c.1524C>T · VCV3984316

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0176%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.07	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -12	GERP -3.9
Overall
CADD	0.313	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0176% South Asian · 16/91,074 alleles

Filtering AF 0.011% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00888%

Overall 0.00167% 27/1,613,926 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0176%	5,692
Admixed American	0.00333%	29,998
African / African-American	0.00134%	74,880
European (non-Finnish)	0.000678%	147,500

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.Thr508=
Coding: c.1524C>T
MANE Select: NM_032043 · reported on NM_001186
Type: single nucleotide variant
Location: chr21:29327348 (GRCh38)
Structure: AlphaFold pLDDT 64.19 · 6 PDB

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

Similar variants

BRIP1 p.Tyr508Asp Uncertain significance ★★ ⚠ same residue
BRIP1 p.Tyr508Cys Uncertain significance ★★ ⚠ same residue
BRIP1 p.Tyr508= Benign/Likely benign ★★ same residue
BACH1 p.Thr508Ser Uncertain significance ★ ⚠ same residue
BRIP1 p.Tyr508Phe Uncertain significance ★ ⚠ same residue
BRIP1 c.1140+1G>A Likely pathogenic ★★ same type
BRIP1 c.1141-2A>C Likely pathogenic ★★ same type
BRIP1 c.1141-2A>G Likely pathogenic ★★ 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-thr508 (accessed [today's date]).

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