Is ABCB7 p.Asn73Ser (c.218A>G) pathogenic?

ABCB7 p.Asn73Ser (c.218A>G) is classified Uncertain significance in ABCB7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-30). AlphaMissense: likely benign (0.0635); Very rare (popmax 0.000337%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ABCB7 p.Asn73Ser (c.218A>G)?

ABCB7 p.Asn73Ser (c.218A>G) is associated with Inborn genetic diseases (ClinVar).

How common is ABCB7 p.Asn73Ser (c.218A>G) in the general population?

ABCB7 p.Asn73Ser (c.218A>G) is very rare (popmax 0.000337%, nfe) (gnomAD).

What do computational predictors say about ABCB7 p.Asn73Ser (c.218A>G)?

AlphaMissense predicts likely benign (score 0.0635) — an in-silico prediction, not a clinical call.

ABCB7 p.Asn73Ser

c.218A>G · VCV4832346

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0635 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000337%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0635	likely benign
REVEL	0.162	moderately benign-leaning
SaProt	LLR -5.00	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP -2.8, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 57 kb · p 0.12 · regional, not allelic
Overall
CADD	3.132	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 0.000337% European (non-Finnish) · 3/889,038 alleles

Filtering AF 9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.5e-05%

Overall 0.000276% 3/1,088,244 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.Asn73Ser
Coding: c.218A>G
MANE Select: NM_001271696
Type: single nucleotide variant
Location: chrX:75114782 (GRCh38)
Structure: AlphaFold pLDDT 78.19 · 4 PDB

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-asn73ser (accessed [today's date]).

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