Is ABCB6 p.Val264Met (c.790G>A) pathogenic?

ABCB6 p.Val264Met (c.790G>A) is classified Uncertain significance in ABCB6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-18). AlphaMissense: likely benign (0.1424); Ultra-rare (popmax 0.0121%, afr); Associated with Inborn genetic diseases.

What condition is associated with ABCB6 p.Val264Met (c.790G>A)?

ABCB6 p.Val264Met (c.790G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ABCB6 p.Val264Met (c.790G>A) in the general population?

ABCB6 p.Val264Met (c.790G>A) is ultra-rare (popmax 0.0121%, afr) (gnomAD).

What do computational predictors say about ABCB6 p.Val264Met (c.790G>A)?

AlphaMissense predicts likely benign (score 0.1424) — an in-silico prediction, not a clinical call.

ABCB6 p.Val264Met

c.790G>A · VCV3292901

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1424 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0121%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1424	likely benign
REVEL	0.17	moderately benign-leaning
SaProt	LLR -5.59	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.25	donor gain · deltas
Constraint at this position
Conservation	phyloP 1.1	GERP -2.4, phastCons 0.41
Regional constraint	o/e 0.96	unconstrained · MANE · 8,732 bp · p 0.15 · regional, not allelic
Overall
CADD	18.66	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 0.0121% African / African-American · 9/74,656 alleles

Filtering AF 0.00625% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00469%

Overall 0.00112% 18/1,606,540 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0121%	8,295
European (non-Finnish)	0.000765%	130,759

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.Val264Met
Coding: c.790G>A
MANE Select: NM_005689
Type: single nucleotide variant
Location: chr2:219216730 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.17 · 16 PDB
Residue 264: an α-helix

Full ABCB6 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

ABCB6 p.Ala57Thr Uncertain significance ★★ ⚠ same condition
ABCB6 p.Ala66Thr Uncertain significance ★★ ⚠ same condition
ABCB6 p.Arg439Cys Uncertain significance ★★ ⚠ same condition
ABCB6 p.Arg450Gln Uncertain significance ★★ ⚠ same condition
ABCB6 p.Arg685His Uncertain significance ★★ ⚠ same condition
ABCB6 p.Arg688Gly Uncertain significance ★★ ⚠ same condition
ABCB6 p.Arg688His Uncertain significance ★★ ⚠ same condition
ABCB6 p.Asn545Ser 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/abcb6-p-val264met (accessed [today's date]).

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