Is ABCB7 p.Leu463Phe (c.1387C>T) pathogenic?

ABCB7 p.Leu463Phe (c.1387C>T) is classified Uncertain significance in ABCB7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-17). AlphaMissense: likely benign (0.2336); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ABCB7 p.Leu463Phe (c.1387C>T)?

ABCB7 p.Leu463Phe (c.1387C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ABCB7 p.Leu463Phe (c.1387C>T) in the general population?

ABCB7 p.Leu463Phe (c.1387C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCB7 p.Leu463Phe (c.1387C>T)?

AlphaMissense predicts likely benign (score 0.2336) — an in-silico prediction, not a clinical call.

ABCB7 p.Leu463Phe

c.1387C>T · rs2081345590 · VCV3125134

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2336 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2336	likely benign
REVEL	0.403	indeterminate
SaProt	LLR -11.70	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	Δ0.24	acceptor loss · deltas
Constraint at this position
Conservation	phyloP 7.2	GERP 1.2, phastCons 1
Regional constraint	o/e 0.51	unconstrained · MANE · 46 kb · p 3.2e-26 · regional, not allelic
Overall
CADD	17.99	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.Leu463Phe
Coding: c.1387C>T
MANE Select: NM_001271696
dbSNP: rs2081345590
Type: single nucleotide variant
Location: chrX:75069433 (GRCh38)
Structure: AlphaFold pLDDT 78.19 · 4 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABCB7 p.Ala5Glu Uncertain significance ★★ ⚠ same condition
ABCB7 p.Asp653Asn Uncertain significance ★★ ⚠ same condition
ABCB7 p.Leu272Phe Uncertain significance ★★ ⚠ same condition
ABCB7 p.Leu395Val Uncertain significance ★★ ⚠ same condition
ABCB7 p.Met175Val Uncertain significance ★★ ⚠ same condition
ABCB7 p.Met441Val Uncertain significance ★★ ⚠ same condition
ABCB7 p.Ser641Leu Uncertain significance ★★ ⚠ same condition
ABCB7 p.Thr187Ala Uncertain significance ★★ ⚠ 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-leu463phe (accessed [today's date]).

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