Is ABCB8 p.Arg406= (c.1218G>A) pathogenic?

ABCB8 p.Arg406= (c.1218G>A) is classified Likely benign in ABCB8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). Ultra-rare (popmax 0.0594%, sas).

How common is ABCB8 p.Arg406= (c.1218G>A) in the general population?

ABCB8 p.Arg406= (c.1218G>A) is ultra-rare (popmax 0.0594%, sas) (gnomAD).

ABCB8 p.Arg406=

c.1218G>A · VCV4107666

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0594%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.337	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.1, phastCons 1
Overall
CADD	17.89	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0594% South Asian · 54/90,856 alleles

Filtering AF 0.0467% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0422%

Overall 0.00707% 114/1,612,582 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.132%	758
South Asiangrpmax	0.0594%	1,683
Remaining individualsnot grpmax-eligible	0.0128%	7,800
Admixed American	0.00335%	29,841
African / African-American	0.00134%	74,808
European (non-Finnish)	0.000848%	117,942

Ashkenazi Jewish 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: ABCB8
Protein: p.Arg406=
Coding: c.1218G>A
MANE Select: NM_007188
Type: single nucleotide variant
Location: chr7:151040268 (GRCh38)
Gene constraint: LOEUF 0.894 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.01 · 2 PDB
Residue 406: the abc transmembrane type-1 domain

Full ABCB8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCB8 c.564+4C>T Benign ★★ same type
ABCB8 p.Ala101= Benign ★★ same type
ABCB8 p.Arg452Leu Benign ★★ ⚠ same type
ABCB8 p.His201= Benign ★★ same type
ABCB8 p.Leu124Val Benign ★★ same type
ABCB8 p.Ser39Asn Benign ★★ ⚠ same type
ABCB8 p.Val110= Benign ★★ same type
ABCB8 p.Val633= Benign ★★ 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/abcb8-p-arg406 (accessed [today's date]).

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