Is ABCB7 p.Ile400Met (c.1200T>G) pathogenic?

ABCB7 p.Ile400Met (c.1200T>G) is classified Pathogenic in ABCB7 (ClinVar, Single submitter, 3 submitters; last evaluated 2012-11-15). AlphaMissense: ambiguous (0.4215); Absent from gnomAD v4.1; Associated with X-linked sideroblastic anemia with ataxia.

What condition is associated with ABCB7 p.Ile400Met (c.1200T>G)?

ABCB7 p.Ile400Met (c.1200T>G) is associated with X-linked sideroblastic anemia with ataxia (ClinVar).

How common is ABCB7 p.Ile400Met (c.1200T>G) in the general population?

ABCB7 p.Ile400Met (c.1200T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCB7 p.Ile400Met (c.1200T>G)?

AlphaMissense predicts ambiguous (score 0.4215) — an in-silico prediction, not a clinical call.

ABCB7 p.Ile400Met

Q: How is X-linked sideroblastic anemia and spinocerebellar ataxia inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1200T>G · rs72554634 · VCV11574

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.4215 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

X-linked sideroblastic anemia with ataxia

Computational evidence

Protein change
AlphaMissense	0.4215	ambiguous
REVEL	0.822	moderately pathogenic-leaning
SaProt	LLR -8.86	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP -1.1, phastCons 1
Regional constraint	o/e 0.51	unconstrained · MANE · 46 kb · p 3.2e-26 · regional, not allelic
Overall
CADD	21.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABCB7
Protein: p.Ile400Met
Coding: c.1200T>G
MANE Select: NM_001271696
dbSNP: rs72554634
Type: single nucleotide variant
Location: chrX:75071516 (GRCh38)
Structure: AlphaFold pLDDT 78.19 · 4 PDB
Residue 400: the abc transmembrane type-1 domain; a UniProt-annotated variant site (in scax6); an α-helix

Full ABCB7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

X-linked sideroblastic anemia with ataxia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For X-linked sideroblastic anemia and spinocerebellar ataxia (Orphanet):

Inheritance: X-linked recessive
Onset: Childhood, Infancy

Similar variants

ABCB7 p.Ile400Asn Uncertain significance ★ ⚠ same residue
ABCB7 p.Ile400Thr Uncertain significance ★ ⚠ same residue
ABCB7 p.Ile400= Benign ★ same residue
ABCB7 c.1935+5G>C Uncertain significance ★★ same condition
ABCB7 c.1032+12A>G Benign/Likely benign ★★ same condition
ABCB7 c.168+69C>G Benign ★★ same condition
ABCB7 c.945-7C>T Benign/Likely benign ★★ same condition
ABCB7 p.Ala580Val Benign/Likely benign ★★ ⚠ 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/abcb7-p-ile400met (accessed [today's date]).

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