Is ABCC6 p.Lys330Ter (c.988A>T) pathogenic?

ABCC6 p.Lys330Ter (c.988A>T) is classified Likely pathogenic in ABCC6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-03). Absent from gnomAD v4.1; Associated with ABCC6-related disorder.

What condition is associated with ABCC6 p.Lys330Ter (c.988A>T)?

ABCC6 p.Lys330Ter (c.988A>T) is associated with ABCC6-related disorder, autosomal recessive inherited pseudoxanthoma elasticum (ClinVar).

How common is ABCC6 p.Lys330Ter (c.988A>T) in the general population?

ABCC6 p.Lys330Ter (c.988A>T) is absent from gnomAD v4.1 (gnomAD).

ABCC6 p.Lys330Ter

c.988A>T · VCV4850038

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

ABCC6-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 8 of 31
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 1.5, 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.Lys330Ter
Coding: c.988A>T
MANE Select: NM_001171
Type: single nucleotide variant
Location: chr16:16203420 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.32 · 4 PDB
Residue 330: the abc transmembrane type-1 1 domain

Full ABCC6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ABCC6-related disorder

Also linked: autosomal recessive inherited pseudoxanthoma elasticum

Similar variants

ABCC6 p.Lys330= Uncertain significance ★ same residue
ABCC6 c.1868-5T>G Pathogenic/Likely pathogenic ★★ same condition
ABCC6 c.2071-1G>A Likely pathogenic ★★ same condition
ABCC6 c.2591-1G>T Likely pathogenic ★★ same condition
ABCC6 c.2787+1G>T Pathogenic ★★ same condition
ABCC6 c.3506+1G>A Pathogenic/Likely 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-lys330ter (accessed [today's date]).

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