Is ABCB7 p.Asn378Asp (c.1132A>G) pathogenic?

ABCB7 p.Asn378Asp (c.1132A>G) is classified Uncertain significance in ABCB7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-11-23). AlphaMissense: likely pathogenic (0.9714); Absent from gnomAD v4.1.

How common is ABCB7 p.Asn378Asp (c.1132A>G) in the general population?

ABCB7 p.Asn378Asp (c.1132A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCB7 p.Asn378Asp (c.1132A>G)?

AlphaMissense predicts likely pathogenic (score 0.9714) — an in-silico prediction, not a clinical call.

ABCB7 p.Asn378Asp

c.1132A>G · rs2147465341 · VCV1334855

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9714 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9714	likely pathogenic
REVEL	0.852	moderately pathogenic-leaning
SaProt	LLR -14.20	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.6, phastCons 1
Regional constraint	o/e 0.51	unconstrained · MANE · 46 kb · p 3.2e-26 · regional, not allelic
Overall
CADD	26.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.Asn378Asp
Coding: c.1132A>G
MANE Select: NM_001271696
dbSNP: rs2147465341
Type: single nucleotide variant
Location: chrX:75071584 (GRCh38)
Structure: AlphaFold pLDDT 78.19 · 4 PDB
Residue 378: the abc transmembrane type-1 domain; a binding site; an α-helix

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

Similar variants

ABCB7 c.1659+5T>G Uncertain significance ★★ same type
ABCB7 c.1935+5G>C Uncertain significance ★★ same type
ABCB7 p.Ala5Glu Uncertain significance ★★ ⚠ same type
ABCB7 p.Arg711His Uncertain significance ★★ ⚠ same type
ABCB7 p.Asp653Asn Uncertain significance ★★ ⚠ same type
ABCB7 p.Glu494Gln Uncertain significance ★★ ⚠ same type
ABCB7 p.Gly197Cys Uncertain significance ★★ ⚠ same type
ABCB7 p.Leu272Phe 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/abcb7-p-asn378asp (accessed [today's date]).

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