Is ABCC6 p.Ser1232fs (c.3692_3693insTT) pathogenic?

ABCC6 p.Ser1232fs (c.36923693insTT) is classified Likely pathogenic in ABCC6 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-03-02). Very rare (popmax 8.47e-05%, nfe); Associated with autosomal recessive inherited pseudoxanthoma elasticum.

What condition is associated with ABCC6 p.Ser1232fs (c.3692_3693insTT)?

ABCC6 p.Ser1232fs (c.3692_3693insTT) is associated with autosomal recessive inherited pseudoxanthoma elasticum (ClinVar).

How common is ABCC6 p.Ser1232fs (c.3692_3693insTT) in the general population?

ABCC6 p.Ser1232fs (c.3692_3693insTT) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is Pseudoxanthoma elasticum inherited?

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

ABCC6 p.Ser1232fs

c.3692_3693insTT · rs779018991 · VCV433513

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

autosomal recessive inherited pseudoxanthoma elasticum

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 26 of 31
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.27	GERP 1.2, phastCons 0.98

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,028 alleles

Overall 6.84e-05% 1/1,461,882 alleles · very rare

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
Protein: p.Ser1232fs
Coding: c.3692_3693insTT
MANE Select: NM_001171
dbSNP: rs779018991
Type: Insertion
Location: chr16:16159524 (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 p.? Pathogenic ★ same condition
ABCC6 p.Ala941fs Likely pathogenic ★ same condition
ABCC6 c.601-11_601-10insGGA Uncertain significance ★ same condition
ABCC6 p.Gln1408fs Likely pathogenic same condition
ABCC6 c.1868-5T>G Pathogenic/Likely pathogenic ★★ same condition
ABCC6 c.2248-2_2248-1del Pathogenic ★★ same condition
ABCC6 c.2591-1G>T Likely pathogenic ★★ same condition
ABCC6 c.2787+1G>T 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-ser1232fs (accessed [today's date]).

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