Is ABCC6 p.Ser321fs (c.960del) pathogenic?

ABCC6 p.Ser321fs (c.960del) is classified Pathogenic in ABCC6 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-03-28). Absent from gnomAD; Associated with arterial calcification, generalized, of infancy, 2.

What condition is associated with ABCC6 p.Ser321fs (c.960del)?

ABCC6 p.Ser321fs (c.960del) is associated with arterial calcification, generalized, of infancy, 2, pseudoxanthoma elasticum, forme fruste, autosomal recessive inherited pseudoxanthoma elasticum (ClinVar).

How common is ABCC6 p.Ser321fs (c.960del) in the general population?

ABCC6 p.Ser321fs (c.960del) is absent from gnomAD (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 p.Ser321fs

c.960del · rs72664226 · VCV433215

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

arterial calcification, generalized, of infancy, 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 8 of 31
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.26	GERP -3, phastCons 0.008
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
Protein: p.Ser321fs
Coding: c.960del
MANE Select: NM_001171
dbSNP: rs72664226
Type: Deletion
Location: chr16:16203448 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.32 · 4 PDB
Residue 321: the abc transmembrane type-1 1 domain

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.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.Leu430fs 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-p-ser321fs (accessed [today's date]).

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