Is ABCB7 p.Val394Ala (c.1181T>C) pathogenic?

ABCB7 p.Val394Ala (c.1181T>C) is classified Uncertain significance in ABCB7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-13). AlphaMissense: likely benign (0.3125); Very rare (popmax 9.11e-05%); Associated with Inborn genetic diseases.

What condition is associated with ABCB7 p.Val394Ala (c.1181T>C)?

ABCB7 p.Val394Ala (c.1181T>C) is associated with Inborn genetic diseases (ClinVar).

How common is ABCB7 p.Val394Ala (c.1181T>C) in the general population?

ABCB7 p.Val394Ala (c.1181T>C) is very rare (popmax 9.11e-05%) (gnomAD).

What do computational predictors say about ABCB7 p.Val394Ala (c.1181T>C)?

AlphaMissense predicts likely benign (score 0.3125) — an in-silico prediction, not a clinical call.

ABCB7 p.Val394Ala

c.1181T>C · VCV3977077

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3125 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 9.11e-05%)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3125	likely benign
REVEL	0.553	indeterminate
SaProt	LLR -7.87	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 0.51	unconstrained · MANE · 46 kb · p 3.2e-26 · regional, not allelic
Overall
CADD	23.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 9.11e-05%

Overall 9.11e-05% 1/1,098,032 alleles · very rare

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: ABCB7
Protein: p.Val394Ala
Coding: c.1181T>C
MANE Select: NM_001271696
Type: single nucleotide variant
Location: chrX:75071535 (GRCh38)
Structure: AlphaFold pLDDT 78.19 · 4 PDB
Residue 394: the abc transmembrane type-1 domain; an α-helix

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-val394ala (accessed [today's date]).

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