Is ABCC6 p.Glu709Ter (c.2125G>T) pathogenic?

ABCC6 p.Glu709Ter (c.2125G>T) is classified Pathogenic in ABCC6 (ClinVar, Single submitter, 2 submitters; last evaluated 2022-12-09). Absent from gnomAD v4.1; Associated with autosomal recessive inherited pseudoxanthoma elasticum.

What condition is associated with ABCC6 p.Glu709Ter (c.2125G>T)?

ABCC6 p.Glu709Ter (c.2125G>T) is associated with autosomal recessive inherited pseudoxanthoma elasticum (ClinVar).

How common is ABCC6 p.Glu709Ter (c.2125G>T) in the general population?

ABCC6 p.Glu709Ter (c.2125G>T) is absent from gnomAD v4.1 (gnomAD).

How is Pseudoxanthoma elasticum inherited?

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

ABCC6 p.Glu709Ter

c.2125G>T · rs114303883 · VCV433454

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

autosomal recessive inherited pseudoxanthoma elasticum

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 17 of 31
Splicing
SpliceAI	Δ0.22	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 4.8	GERP 0.83, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABCC6
Protein: p.Glu709Ter
Coding: c.2125G>T
MANE Select: NM_001171
dbSNP: rs114303883
Type: single nucleotide variant
Location: chr16:16182534 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.32 · 4 PDB
Residue 709: a UniProt-annotated variant site (found in patient with putative diagnosis of pex; uncertain significance; loss-of-function mutation; localization comparable to wild-type); an α-helix; the abc transporter 1 domain

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.Glu709Lys Uncertain significance ★★ ⚠ same residue
ABCC6 p.Glu709Gly Uncertain significance ⚠ same residue
ABCC6 p.Glu709Gln Uncertain significance ★ ⚠ same residue
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

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-glu709ter (accessed [today's date]).

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