Is BACH1 p.Ile498Phe (c.1492A>T) pathogenic?

BACH1 p.Ile498Phe (c.1492A>T) is classified Benign in BACH1 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2021-04-06). AlphaMissense: likely benign (0.1999); Rare (popmax 0.594%, mid); Associated with BACH1-related disorder.

What condition is associated with BACH1 p.Ile498Phe (c.1492A>T)?

BACH1 p.Ile498Phe (c.1492A>T) is associated with BACH1-related disorder (ClinVar).

How common is BACH1 p.Ile498Phe (c.1492A>T) in the general population?

BACH1 p.Ile498Phe (c.1492A>T) is rare (popmax 0.594%, mid) (gnomAD).

What do computational predictors say about BACH1 p.Ile498Phe (c.1492A>T)?

AlphaMissense predicts likely benign (score 0.1999) — an in-silico prediction, not a clinical call.

BACH1 p.Ile498Phe

c.1492A>T · rs151321858 · VCV3034851

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1999 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.594%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

BACH1-related disorder

Computational evidence

Protein change
AlphaMissense	0.1999	likely benign
REVEL	0.322	indeterminate
SaProt	LLR -6.02	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.45	acceptor gain · deltas
Pangolin	Δ0.39	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Overall
CADD	32.0	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 0.594% Middle Eastern · 36/6,062 alleles

Filtering AF 0.441% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.388%

Overall 0.0995% 1,606/1,614,244 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	2.17%	46
Middle Easterngrpmax	0.594%	168
Admixed American	0.258%	387
Remaining individualsnot grpmax-eligible	0.238%	420
South Asian	0.169%	591
African / African-American	0.0719%	1,390
European (non-Finnish)	0.0353%	2,837
Finnishnot grpmax-eligible	0.00156%	64,034

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: BACH1
Protein: p.Ile498Phe
Coding: c.1492A>T
MANE Select: NM_032043 · reported on NM_001186
dbSNP: rs151321858
Type: single nucleotide variant
Location: chr21:29327316 (GRCh38)
Structure: AlphaFold pLDDT 64.19 · 6 PDB

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

Disease context

BACH1-related disorder

Similar variants

BRIP1 p.Leu498His Uncertain significance ★★ ⚠ same residue
BRIP1 p.Leu498Ile Uncertain significance ★★ ⚠ same residue
BRIP1 c.918+1G>A Pathogenic/Likely pathogenic ★★ same condition
BRIP1 p.Arg798Ter Pathogenic/Likely pathogenic ★★ same condition
BRIP1 p.Gln414Ter Pathogenic/Likely pathogenic ★★ same condition
BRIP1 p.Gln499Ter Pathogenic/Likely pathogenic ★★ same condition
BRIP1 p.Ser624Ter Pathogenic/Likely pathogenic ★★ same condition
BRIP1 p.Tyr748Ter Pathogenic/Likely pathogenic ★★ 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/bach1-p-ile498phe (accessed [today's date]).

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