Is ABCC6 c.998+2del pathogenic?

ABCC6 c.998+2del is classified Likely pathogenic in ABCC6 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-03-02). Absent from gnomAD; Associated with autosomal recessive inherited pseudoxanthoma elasticum.

What condition is associated with ABCC6 c.998+2del?

ABCC6 c.998+2del is associated with autosomal recessive inherited pseudoxanthoma elasticum (ClinVar).

How common is ABCC6 c.998+2del in the general population?

ABCC6 c.998+2del is absent from gnomAD (gnomAD).

How is Pseudoxanthoma elasticum inherited?

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

ABCC6 c.998+2del

rs72664205 · VCV433398

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

canonical splice-site (±1/±2)

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

autosomal recessive inherited pseudoxanthoma elasticum

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	canonical splice-site (±1/±2)	predicted loss-of-function
Splicing
Splice region	donor +2	canonical splice dinucleotide (donor +2) · inside the BP7-excluded zone
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.7	GERP -3
Non-coding constraint	Z 0.30	1 kb window · o/e 0.98 · regional · uncalibrated
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ABCC6
Coding: c.998+2del
MANE Select: NM_001171
dbSNP: rs72664205
Type: Deletion
Location: chr16:16203408 (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

For Pseudoxanthoma elasticum (Orphanet):

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

Similar variants

ABCC6 c.2248-2_2248-1del Pathogenic ★★ same condition
ABCC6 c.3506+2_3506+5del Pathogenic/Likely pathogenic ★★ same condition
ABCC6 c.998+2_998+3del Pathogenic/Likely pathogenic ★★ same condition
ABCC6 p.Ala667fs Pathogenic/Likely pathogenic ★★ same condition
ABCC6 p.Arg473fs Pathogenic/Likely pathogenic ★★ same condition
ABCC6 p.Asp1368fs Pathogenic ★★ same condition
ABCC6 p.Glu559fs Pathogenic/Likely pathogenic ★★ same condition
ABCC6 p.Leu775fs 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-998-plus-2del (accessed [today's date]).

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