Is ABCC6 c.3306+5G>A pathogenic?

ABCC6 c.3306+5G>A is classified Uncertain significance in ABCC6 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-06-25). Ultra-rare (popmax 0.0384%, sas); Associated with arterial calcification, generalized, of infancy, 2.

What condition is associated with ABCC6 c.3306+5G>A?

ABCC6 c.3306+5G>A is associated with arterial calcification, generalized, of infancy, 2, pseudoxanthoma elasticum, forme fruste, autosomal recessive inherited pseudoxanthoma elasticum (ClinVar).

How common is ABCC6 c.3306+5G>A in the general population?

ABCC6 c.3306+5G>A is ultra-rare (popmax 0.0384%, sas) (gnomAD).

How is Generalized arterial calcification of infancy inherited?

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

ABCC6 c.3306+5G>A

rs369806278 · VCV1001250

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0384%, sas)

Conditions

arterial calcification, generalized, of infancy, 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +5	donor splice region (+5, within the first 6 intronic nt) · inside the BP7-excluded zone
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.77	GERP 0.57
Non-coding constraint	Z 2.47	1 kb window · o/e 0.82 · regional · uncalibrated
Overall
CADD	22.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0384% South Asian · 35/91,074 alleles

Filtering AF 0.0283% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0249%

Overall 0.0182% 293/1,613,002 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0384%	2,602
Remaining individualsnot grpmax-eligible	0.0272%	3,676
European (non-Finnish)	0.0198%	5,043
African / African-American	0.00533%	18,758
East Asian	0.00446%	22,439
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606

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.3306+5G>A
MANE Select: NM_001171
dbSNP: rs369806278
Type: single nucleotide variant
Location: chr16:16165618 (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

arterial calcification, generalized, of infancy, 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pseudoxanthoma elasticum, forme fruste autosomal recessive inherited pseudoxanthoma elasticum

For Generalized arterial calcification of infancy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Antenatal, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Worldwide)

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-3306-plus-5g-a (accessed [today's date]).

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