Is ABCB6 p.Arg276Trp (c.826C>T) pathogenic?

ABCB6 p.Arg276Trp (c.826C>T) is classified Benign/Likely benign in ABCB6 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-03). AlphaMissense: likely pathogenic (0.9082); Low-frequency (popmax 1.44%, nfe); Associated with hereditary coproporphyria.

What condition is associated with ABCB6 p.Arg276Trp (c.826C>T)?

ABCB6 p.Arg276Trp (c.826C>T) is associated with hereditary coproporphyria, acute intermittent porphyria, variegate porphyria (ClinVar).

How common is ABCB6 p.Arg276Trp (c.826C>T) in the general population?

ABCB6 p.Arg276Trp (c.826C>T) is low-frequency (popmax 1.44%, nfe) (gnomAD).

How is Hereditary coproporphyria inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about ABCB6 p.Arg276Trp (c.826C>T)?

AlphaMissense predicts likely pathogenic (score 0.9082) — an in-silico prediction, not a clinical call.

ABCB6 p.Arg276Trp

c.826C>T · rs57467915 · VCV235291

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely pathogenic

0.9082 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.44%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary coproporphyria

Computational evidence

Protein change
AlphaMissense	0.9082	likely pathogenic
REVEL	0.723	pathogenic-leaning
SaProt	LLR -16.16	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.29 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.3	GERP -1.2, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 8,732 bp · p 0.15 · regional, not allelic
Overall
CADD	25.9	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 1.44% European (non-Finnish) · 16,744/1,166,268 alleles

Filtering AF 1.42% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.41%

Overall 1.22% 19,392/1,585,890 alleles · low-frequency

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.98%	50
Amishnot grpmax-eligible	1.97%	51
European (non-Finnish)grpmax	1.44%	70
Remaining individualsnot grpmax-eligible	0.973%	103
Ashkenazi Jewishnot grpmax-eligible	0.551%	181
Admixed American	0.4%	250
South Asian	0.26%	384
African / African-American	0.244%	410
Middle Eastern	0.116%	862
East Asian	0.00696%	14,375

Finnish 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: ABCB6
Protein: p.Arg276Trp
Coding: c.826C>T
MANE Select: NM_005689
dbSNP: rs57467915
Type: single nucleotide variant
Location: chr2:219216694 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.17 · 16 PDB
Residue 276: the abc transmembrane type-1 domain; a UniProt-annotated variant site (may be a modifier of disease severity in porphyria patients; loss of expression); an α-helix

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

Disease context

hereditary coproporphyria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: acute intermittent porphyria variegate porphyria protoporphyria, erythropoietic, 1

For Hereditary coproporphyria (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

ABCB6 p.Arg276Gln Uncertain significance ★ ⚠ same residue
ABCB6 p.Arg276Pro Uncertain significance ★ ⚠ same residue
ABCB6 p.Ala492Thr Benign/Likely benign ★★ ⚠ same condition
ABCB6 p.Arg192Trp Benign/Likely benign ★★ ⚠ same condition
ABCB6 p.Arg247Cys Benign/Likely benign ★★ same condition
ABCB6 p.Arg343Gln Benign/Likely benign ★★ same condition
ABCB6 p.Thr521Ser Benign/Likely benign ★★ same condition
ABCB6 p.Arg192Gln Conflicting classifications of pathogenicity ★ ⚠ 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-arg276trp (accessed [today's date]).

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