Is ABCB6 p.Arg343Gln (c.1028G>A) pathogenic?

ABCB6 p.Arg343Gln (c.1028G>A) is classified Benign/Likely benign in ABCB6 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.1171); Common (popmax 15.3%, afr) — too common for a highly-penetrant pathogenic allele; Associated with protoporphyria, erythropoietic, 1.

What condition is associated with ABCB6 p.Arg343Gln (c.1028G>A)?

ABCB6 p.Arg343Gln (c.1028G>A) is associated with protoporphyria, erythropoietic, 1, acute intermittent porphyria (ClinVar).

How is Autosomal erythropoietic protoporphyria inherited?

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

What do computational predictors say about ABCB6 p.Arg343Gln (c.1028G>A)?

AlphaMissense predicts likely benign (score 0.1171) — an in-silico prediction, not a clinical call.

ABCB6 p.Arg343Gln

Q: How common is ABCB6 p.Arg343Gln (c.1028G>A) in the general population?

ABCB6 p.Arg343Gln (c.1028G>A) is common (popmax 15.3%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1028G>A · rs60322991 · VCV1227694

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1171 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 15.3%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

protoporphyria, erythropoietic, 1

Computational evidence

Protein change
AlphaMissense	0.1171	likely benign
REVEL	0.432	indeterminate
SaProt	LLR -8.85	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 0.054, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 8,732 bp · p 0.15 · regional, not allelic
Overall
CADD	20.9	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 15.3% African / African-American · 11,459/74,692 alleles

Filtering AF 15.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 15%

Overall 0.83% 13,271/1,598,210 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	15.3%	7
Remaining individualsnot grpmax-eligible	1.17%	86
Admixed American	1.09%	92
Middle Eastern	0.632%	158
South Asian	0.106%	944
European (non-Finnish)	0.0278%	3,599
East Asian	0.00905%	11,045
Ashkenazi Jewishnot grpmax-eligible	0.00342%	29,226

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.Arg343Gln
Coding: c.1028G>A
MANE Select: NM_005689
dbSNP: rs60322991
Type: single nucleotide variant
Location: chr2:219216123 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.17 · 16 PDB
Residue 343: the abc transmembrane type-1 domain; a UniProt-annotated variant site (in); an α-helix

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

Disease context

protoporphyria, erythropoietic, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: acute intermittent porphyria

For Autosomal erythropoietic protoporphyria (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

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.Arg276Trp Benign/Likely benign ★★ same condition
ABCB6 p.Thr521Ser Benign/Likely benign ★★ same condition
ABCB6 p.Arg192Gln Conflicting classifications of pathogenicity ★ ⚠ same condition
ABCB6 p.Gly588Ser Conflicting classifications of pathogenicity ★ ⚠ same condition
ABCB6 p.Gly729Ser 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-arg343gln (accessed [today's date]).

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