Is ABCB6 p.Leu246= (c.738C>G) pathogenic?

ABCB6 p.Leu246= (c.738C>G) is classified Likely benign in ABCB6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-31). Ultra-rare (popmax 0.0267%, amr).

How common is ABCB6 p.Leu246= (c.738C>G) in the general population?

ABCB6 p.Leu246= (c.738C>G) is ultra-rare (popmax 0.0267%, amr) (gnomAD).

ABCB6 p.Leu246=

c.738C>G · rs566841625 · VCV2890569

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.051	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.17	GERP -3.9, phastCons 0.83
Overall
CADD	6.094	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0267% Admixed American · 16/59,918 alleles

Filtering AF 0.0167% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.0013% 21/1,612,770 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0267%	3,745
Remaining individualsnot grpmax-eligible	0.00801%	12,492

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: ABCB6
Protein: p.Leu246=
Coding: c.738C>G
MANE Select: NM_005689
dbSNP: rs566841625
Type: single nucleotide variant
Location: chr2:219216782 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.17 · 16 PDB
Residue 246: an α-helix

Full ABCB6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCB6 p.Ala164Thr Uncertain significance ★★ ⚠ same type
ABCB6 p.Ala57Thr Uncertain significance ★★ ⚠ same type
ABCB6 p.Ala66Thr Uncertain significance ★★ ⚠ same type
ABCB6 p.Ala681Thr Uncertain significance ★★ ⚠ same type
ABCB6 p.Arg135Ser Uncertain significance ★★ ⚠ same type
ABCB6 p.Arg439Cys Uncertain significance ★★ ⚠ same type
ABCB6 p.Arg450Gln Uncertain significance ★★ ⚠ same type
ABCB6 p.Arg685His 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/abcb6-p-leu246 (accessed [today's date]).

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