Is ABCB7 p.Ile222Val (c.664A>G) pathogenic?

ABCB7 p.Ile222Val (c.664A>G) is classified Benign in ABCB7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-11). AlphaMissense: likely benign (0.2049); Ultra-rare (popmax 0.0208%, eas).

How common is ABCB7 p.Ile222Val (c.664A>G) in the general population?

ABCB7 p.Ile222Val (c.664A>G) is ultra-rare (popmax 0.0208%, eas) (gnomAD).

What do computational predictors say about ABCB7 p.Ile222Val (c.664A>G)?

AlphaMissense predicts likely benign (score 0.2049) — an in-silico prediction, not a clinical call.

ABCB7 p.Ile222Val

c.664A>G · VCV4750500

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2049 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0208%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2049	likely benign
REVEL	0.463	indeterminate
SaProt	LLR -7.20	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 2, phastCons 1
Regional constraint	o/e 0.51	unconstrained · MANE · 46 kb · p 3.2e-26 · regional, not allelic
Overall
CADD	21.1	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 0.0208% East Asian · 7/33,713 alleles

Filtering AF 0.00969% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00681%

Overall 0.00215% 26/1,209,212 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0208%	4,816
South Asian	0.0158%	6,312
Admixed American	0.0109%	9,135
Remaining individualsnot grpmax-eligible	0.0042%	23,798
European (non-Finnish)	0.000335%	298,223

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.Ile222Val
Coding: c.664A>G
MANE Select: NM_001271696
Type: single nucleotide variant
Location: chrX:75075553 (GRCh38)
Structure: AlphaFold pLDDT 78.19 · 4 PDB
Residue 222: the abc transmembrane type-1 domain; 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.Asn378Asp 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

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-ile222val (accessed [today's date]).

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