Is ABCB7 p.Ile591Val (c.1771A>G) pathogenic?

ABCB7 p.Ile591Val (c.1771A>G) is classified Uncertain significance in ABCB7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-03). AlphaMissense: likely benign (0.0831); Very rare (popmax 0.00353%, sas).

How common is ABCB7 p.Ile591Val (c.1771A>G) in the general population?

ABCB7 p.Ile591Val (c.1771A>G) is very rare (popmax 0.00353%, sas) (gnomAD).

What do computational predictors say about ABCB7 p.Ile591Val (c.1771A>G)?

AlphaMissense predicts likely benign (score 0.0831) — an in-silico prediction, not a clinical call.

ABCB7 p.Ile591Val

c.1771A>G · rs2081308033 · VCV2581356

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0831 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00353%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0831	likely benign
REVEL	0.52	indeterminate
SaProt	LLR -5.75	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 4.2	GERP 0.45, phastCons 1
Regional constraint	o/e 0.51	unconstrained · MANE · 46 kb · p 3.2e-26 · regional, not allelic
Overall
CADD	19.84	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 0.00353% South Asian · 2/56,735 alleles

Filtering AF 0.000585% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000412%

Overall 0.000992% 12/1,209,088 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00353%	28,368
European (non-Finnish)	0.00112%	89,483

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.Ile591Val
Coding: c.1771A>G
MANE Select: NM_001271696
dbSNP: rs2081308033
Type: single nucleotide variant
Location: chrX:75065130 (GRCh38)
Structure: AlphaFold pLDDT 78.19 · 4 PDB
Residue 591: the abc transporter domain; an α-helix

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

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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-ile591val (accessed [today's date]).

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