Is ABCB7 p.Ile392Val (c.1174A>G) pathogenic?

ABCB7 p.Ile392Val (c.1174A>G) is classified Benign/Likely benign in ABCB7 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-22). AlphaMissense: likely benign (0.0829); Ultra-rare (popmax 0.0445%, nfe); Associated with intellectual disability.

What condition is associated with ABCB7 p.Ile392Val (c.1174A>G)?

ABCB7 p.Ile392Val (c.1174A>G) is associated with intellectual disability (ClinVar).

How common is ABCB7 p.Ile392Val (c.1174A>G) in the general population?

ABCB7 p.Ile392Val (c.1174A>G) is ultra-rare (popmax 0.0445%, nfe) (gnomAD).

What do computational predictors say about ABCB7 p.Ile392Val (c.1174A>G)?

AlphaMissense predicts likely benign (score 0.0829) — an in-silico prediction, not a clinical call.

ABCB7 p.Ile392Val

c.1174A>G · rs139311518 · VCV213976

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0829 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0445%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

intellectual disability

Computational evidence

Protein change
AlphaMissense	0.0829	likely benign
REVEL	0.306	indeterminate
SaProt	LLR -6.59	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 2.8	GERP 0.38, phastCons 1
Regional constraint	o/e 0.51	unconstrained · MANE · 46 kb · p 3.2e-26 · regional, not allelic
Overall
CADD	15.54	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 0.0445% European (non-Finnish) · 398/895,148 alleles

Filtering AF 0.0408% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0394%

Overall 0.0363% 439/1,209,570 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0451%	2,216
European (non-Finnish)grpmax	0.0445%	2,249
Remaining individualsnot grpmax-eligible	0.0252%	3,966
Ashkenazi Jewishnot grpmax-eligible	0.00908%	11,010
African / African-American	0.00526%	19,026
South Asian	0.00352%	28,382
Admixed American	0.00219%	45,635

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ile392Val
Coding: c.1174A>G
MANE Select: NM_001271696
dbSNP: rs139311518
Type: single nucleotide variant
Location: chrX:75071542 (GRCh38)
Structure: AlphaFold pLDDT 78.19 · 4 PDB
Residue 392: 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

intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-ile392val (accessed [today's date]).

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