Is ABCC6 p.Arg940= (c.2820T>G) pathogenic?

ABCC6 p.Arg940= (c.2820T>G) is classified Likely benign in ABCC6 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-09-13). Ultra-rare (popmax 0.054%, amr); Associated with autosomal recessive inherited pseudoxanthoma elasticum.

What condition is associated with ABCC6 p.Arg940= (c.2820T>G)?

ABCC6 p.Arg940= (c.2820T>G) is associated with autosomal recessive inherited pseudoxanthoma elasticum (ClinVar).

How common is ABCC6 p.Arg940= (c.2820T>G) in the general population?

ABCC6 p.Arg940= (c.2820T>G) is ultra-rare (popmax 0.054%, amr) (gnomAD).

How is Pseudoxanthoma elasticum inherited?

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

ABCC6 p.Arg940=

c.2820T>G · rs72664286 · VCV433289

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.054%, amr)

Conditions

autosomal recessive inherited pseudoxanthoma elasticum

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.25	GERP -1.9
Overall
CADD	1.224	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.054% Admixed American · 28/51,858 alleles

Filtering AF 0.0383% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.033%

Overall 0.00186% 29/1,560,834 alleles · ultra-rare exomes 25/1,408,672 · genomes 4/152,162 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.054%	1,852
Remaining individualsnot grpmax-eligible	0.00165%	60,528

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.Arg940=
Coding: c.2820T>G
MANE Select: NM_001171
dbSNP: rs72664286
Type: single nucleotide variant
Location: chr16:16169821 (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.Arg940Cys Uncertain significance ★★ ⚠ same residue
ABCC6 p.Arg940His Uncertain significance ★ ⚠ same residue
ABCC6 p.Arg940Ser 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-arg940 (accessed [today's date]).

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