Is ABCB7 p.Ile320Val (c.958A>G) pathogenic?

ABCB7 p.Ile320Val (c.958A>G) is classified Conflicting classifications of pathogenicity in ABCB7 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-10-09). AlphaMissense: likely benign (0.1021); Ultra-rare (popmax 0.0926%, afr); Associated with Inborn genetic diseases.

What condition is associated with ABCB7 p.Ile320Val (c.958A>G)?

ABCB7 p.Ile320Val (c.958A>G) is associated with Inborn genetic diseases (ClinVar).

How common is ABCB7 p.Ile320Val (c.958A>G) in the general population?

ABCB7 p.Ile320Val (c.958A>G) is ultra-rare (popmax 0.0926%, afr) (gnomAD).

What do computational predictors say about ABCB7 p.Ile320Val (c.958A>G)?

AlphaMissense predicts likely benign (score 0.1021) — an in-silico prediction, not a clinical call.

ABCB7 p.Ile320Val

c.958A>G · rs1133578 · VCV1197079

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1021 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0926%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1021	likely benign
REVEL	0.331	indeterminate
SaProt	LLR -5.57	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 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	18.21	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

Grpmax group 0.0926% African / African-American · 53/57,231 alleles

Filtering AF 0.0727% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0656%

Overall 0.00508% 61/1,201,182 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0926%	1,080
Admixed American	0.0109%	9,155
Remaining individualsnot grpmax-eligible	0.00634%	15,777

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.Ile320Val
Coding: c.958A>G
MANE Select: NM_001271696
dbSNP: rs1133578
Type: single nucleotide variant
Location: chrX:75073763 (GRCh38)
Structure: AlphaFold pLDDT 78.19 · 4 PDB
Residue 320: 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-ile320val (accessed [today's date]).

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