Is ABCB6 p.Arg344Trp (c.1030C>T) pathogenic?

ABCB6 p.Arg344Trp (c.1030C>T) is classified Uncertain significance in ABCB6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-22). AlphaMissense: likely benign (0.1801); Very rare (popmax 0.00454%, eas); Associated with Inborn genetic diseases.

What condition is associated with ABCB6 p.Arg344Trp (c.1030C>T)?

ABCB6 p.Arg344Trp (c.1030C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ABCB6 p.Arg344Trp (c.1030C>T) in the general population?

ABCB6 p.Arg344Trp (c.1030C>T) is very rare (popmax 0.00454%, eas) (gnomAD).

What do computational predictors say about ABCB6 p.Arg344Trp (c.1030C>T)?

AlphaMissense predicts likely benign (score 0.1801) — an in-silico prediction, not a clinical call.

ABCB6 p.Arg344Trp

c.1030C>T · rs1256856094 · VCV2621409

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1801 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00454%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1801	likely benign
REVEL	0.463	indeterminate
SaProt	LLR -11.18	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	Δ0.42	donor gain · deltas
Constraint at this position
Conservation	phyloP 1.7	GERP -2.8, phastCons 0.005
Regional constraint	o/e 0.96	unconstrained · MANE · 8,732 bp · p 0.15 · regional, not allelic
Overall
CADD	24.0	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 0.00454% East Asian · 2/44,070 alleles

Filtering AF 0.000752% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000281%

Overall 0.000877% 14/1,596,736 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00454%	22,035
Admixed American	0.00173%	57,696
Remaining individualsnot grpmax-eligible	0.00162%	61,800
African / African-American	0.00134%	74,728
European (non-Finnish)	0.000768%	130,276

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.Arg344Trp
Coding: c.1030C>T
MANE Select: NM_005689
dbSNP: rs1256856094
Type: single nucleotide variant
Location: chr2:219216121 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.17 · 16 PDB
Residue 344: the abc transmembrane type-1 domain; 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-arg344trp (accessed [today's date]).

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