Is ABCC6 p.Pro945= (c.2835C>T) pathogenic?

ABCC6 p.Pro945= (c.2835C>T) is classified Benign in ABCC6 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). Common (popmax 25.1%, eas) — too common for a highly-penetrant pathogenic allele; Associated with pseudoxanthoma elasticum, forme fruste.

What condition is associated with ABCC6 p.Pro945= (c.2835C>T)?

ABCC6 p.Pro945= (c.2835C>T) is associated with pseudoxanthoma elasticum, forme fruste, autosomal recessive inherited pseudoxanthoma elasticum, arterial calcification, generalized, of infancy, 2 (ClinVar).

ABCC6 p.Pro945=

Q: How common is ABCC6 p.Pro945= (c.2835C>T) in the general population?

ABCC6 p.Pro945= (c.2835C>T) is common (popmax 25.1%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2835C>T · rs2856585 · VCV433292

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 25.1%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

pseudoxanthoma elasticum, forme fruste

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 -10	GERP -3
Overall
CADD	0.088	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 25.1% East Asian · 10,597/42,282 alleles

Filtering AF 24.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 24.5%

Overall 7.16% 112,514/1,571,388 alleles · common exomes 98,791/1,419,112 · genomes 13,723/152,276 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	25.1%	4
African / African-American	12.4%	8
Admixed American	9.91%	10
Middle Eastern	8.76%	11
Amishnot grpmax-eligible	8.24%	12
Remaining individualsnot grpmax-eligible	7.5%	13
Ashkenazi Jewishnot grpmax-eligible	7.2%	14
Finnishnot grpmax-eligible	6.49%	15
South Asian	6.42%	16
European (non-Finnish)	6.11%	16

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.Pro945=
Coding: c.2835C>T
MANE Select: NM_001171
dbSNP: rs2856585
Type: single nucleotide variant
Location: chr16:16169806 (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

pseudoxanthoma elasticum, forme fruste — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive inherited pseudoxanthoma elasticum arterial calcification, generalized, of infancy, 2

Similar variants

ABCC6 p.Pro945Leu 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
ABCC6 c.3736-1G>A Pathogenic ★★ same condition
ABCC6 c.3883-6G>A Pathogenic/Likely 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-pro945 (accessed [today's date]).

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