Is ABCC6 c.4208+9G>A pathogenic?

ABCC6 c.4208+9G>A is classified Benign/Likely benign in ABCC6 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-04). Low-frequency (popmax 4.16%, sas); Associated with autosomal recessive inherited pseudoxanthoma elasticum.

What condition is associated with ABCC6 c.4208+9G>A?

ABCC6 c.4208+9G>A is associated with autosomal recessive inherited pseudoxanthoma elasticum, pseudoxanthoma elasticum, forme fruste, arterial calcification, generalized, of infancy, 2 (ClinVar).

How common is ABCC6 c.4208+9G>A in the general population?

ABCC6 c.4208+9G>A is low-frequency (popmax 4.16%, sas) (gnomAD).

How is Pseudoxanthoma elasticum inherited?

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

ABCC6 c.4208+9G>A

rs58760581 · VCV433396

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.16%, sas)

Conditions

autosomal recessive inherited pseudoxanthoma elasticum

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +9	near-intronic (+9 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.4	GERP -2.3
Non-coding constraint	Z 3.13	1 kb window · o/e 0.78 · regional · uncalibrated
Overall
CADD	0.015	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.16% South Asian · 3,786/90,932 alleles

Filtering AF 4.05% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.01%

Overall 1.73% 27,830/1,611,610 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	4.16%	24
Middle Eastern	3.32%	30
European (non-Finnish)	1.79%	56
Remaining individualsnot grpmax-eligible	1.72%	58
Ashkenazi Jewishnot grpmax-eligible	1.43%	70
Finnishnot grpmax-eligible	1.13%	88
Amishnot grpmax-eligible	0.987%	101
Admixed American	0.6%	167
African / African-American	0.296%	338
East Asian	0.029%	3,451

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: ABCC6
Coding: c.4208+9G>A
MANE Select: NM_001171
dbSNP: rs58760581
Type: single nucleotide variant
Location: chr16:16154619 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.32 · 4 PDB

Full ABCC6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive inherited pseudoxanthoma elasticum — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pseudoxanthoma elasticum, forme fruste arterial calcification, generalized, of infancy, 2

For Pseudoxanthoma elasticum (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

ABCC6 c.1868-5T>G Pathogenic/Likely pathogenic ★★ same condition
ABCC6 c.2591-1G>T Likely pathogenic ★★ same condition
ABCC6 c.2787+1G>T Pathogenic ★★ same condition
ABCC6 c.3507-1G>A Pathogenic ★★ same condition
ABCC6 c.37-1G>A Pathogenic ★★ same condition
ABCC6 c.3736-1G>A Pathogenic ★★ same condition
ABCC6 c.3883-6G>A Pathogenic/Likely pathogenic ★★ same condition
ABCC6 c.4209-2A>C Pathogenic/Likely pathogenic ★★ 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/abcc6-c-4208-plus-9g-a (accessed [today's date]).

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