Is ABCC6 p.Arg1030Ter (c.3088C>T) pathogenic?

ABCC6 p.Arg1030Ter (c.3088C>T) is classified Pathogenic/Likely pathogenic in ABCC6 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-11-05). Very rare (popmax 0.00768%, sas); Associated with ABCC6-related disorder.

What condition is associated with ABCC6 p.Arg1030Ter (c.3088C>T)?

ABCC6 p.Arg1030Ter (c.3088C>T) is associated with ABCC6-related disorder, autosomal recessive inherited pseudoxanthoma elasticum (ClinVar).

How common is ABCC6 p.Arg1030Ter (c.3088C>T) in the general population?

ABCC6 p.Arg1030Ter (c.3088C>T) is very rare (popmax 0.00768%, sas) (gnomAD).

ABCC6 p.Arg1030Ter

c.3088C>T · rs72653705 · VCV433300

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00768%, sas)

Conditions

ABCC6-related disorder

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 23 of 31
Splicing
SpliceAI	Δ0.36	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 4.4	GERP -2, phastCons 0.92
Overall
CADD	46.0	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

Grpmax group 0.00768% South Asian · 7/91,090 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.00316% 51/1,613,370 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00768%	13,013
European (non-Finnish)	0.00347%	28,781
Admixed American	0.00167%	60,022
Remaining individualsnot grpmax-eligible	0.0016%	62,500
African / African-American	0.00133%	75,056

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.Arg1030Ter
Coding: c.3088C>T
MANE Select: NM_001171
dbSNP: rs72653705
Type: single nucleotide variant
Location: chr16:16165841 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.32 · 4 PDB
Residue 1030: the abc transmembrane type-1 2 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.Arg1030Gly Uncertain significance ★ ⚠ same residue
ABCC6 p.Arg1030Pro 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

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-arg1030ter (accessed [today's date]).

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