Is ABCC6 p.Arg1141Ter (c.3421C>T) pathogenic?

ABCC6 p.Arg1141Ter (c.3421C>T) is classified Pathogenic in ABCC6 (ClinVar, Multiple submitters, 39 submitters; last evaluated 2026-07-02). Rare (popmax 0.194%, nfe); Associated with ABCC6-related disorder.

What condition is associated with ABCC6 p.Arg1141Ter (c.3421C>T)?

ABCC6 p.Arg1141Ter (c.3421C>T) is associated with ABCC6-related disorder, pseudoxanthoma elasticum, forme fruste, autosomal recessive inherited pseudoxanthoma elasticum (ClinVar).

How common is ABCC6 p.Arg1141Ter (c.3421C>T) in the general population?

ABCC6 p.Arg1141Ter (c.3421C>T) is rare (popmax 0.194%, nfe) (gnomAD).

ABCC6 p.Arg1141Ter

c.3421C>T · rs72653706 · VCV6559

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 39 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.194%, nfe)

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 24 of 31
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP 0.57, phastCons 1
Overall
CADD	41.0	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 0.194% European (non-Finnish) · 2,293/1,180,030 alleles

Filtering AF 0.188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.185%

Overall 0.161% 2,603/1,613,922 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.264%	379
European (non-Finnish)grpmax	0.194%	515
Remaining individualsnot grpmax-eligible	0.134%	744
Middle Eastern	0.0495%	2,021
Admixed American	0.0433%	2,309
African / African-American	0.0266%	3,753
South Asian	0.00878%	11,386
East Asian	0.00223%	44,884

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg1141Ter
Coding: c.3421C>T
MANE Select: NM_001171
dbSNP: rs72653706
Type: single nucleotide variant
Location: chr16:16163078 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.32 · 4 PDB
Residue 1141: 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: pseudoxanthoma elasticum, forme fruste autosomal recessive inherited pseudoxanthoma elasticum arterial calcification, generalized, of infancy, 2 cutis laxa pseudoxanthoma elasticum (inherited or acquired)inherited pseudoxanthoma elasticum

Similar variants

ABCC6 p.Arg1141Gln Likely benign ★★ 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-arg1141ter (accessed [today's date]).

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