Is ABCC6 p.Ala830= (c.2490C>T) pathogenic?

ABCC6 p.Ala830= (c.2490C>T) is classified Benign in ABCC6 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-04). Common (popmax 25.6%, afr) — too common for a highly-penetrant pathogenic allele; Associated with autosomal recessive inherited pseudoxanthoma elasticum.

What condition is associated with ABCC6 p.Ala830= (c.2490C>T)?

ABCC6 p.Ala830= (c.2490C>T) is associated with autosomal recessive inherited pseudoxanthoma elasticum, pseudoxanthoma elasticum, forme fruste, arterial calcification, generalized, of infancy, 2 (ClinVar).

How is Pseudoxanthoma elasticum inherited?

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

ABCC6 p.Ala830=

Q: How common is ABCC6 p.Ala830= (c.2490C>T) in the general population?

ABCC6 p.Ala830= (c.2490C>T) is common (popmax 25.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2490C>T · rs9924755 · VCV433280

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 25.6%, afr) — too common for a highly-penetrant pathogenic allele

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 1.7	GERP -3.7, phastCons 0.85
Overall
CADD	6.633	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 25.6% African / African-American · 19,173/75,008 alleles

Filtering AF 25.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 25.1%

Overall 14.7% 236,741/1,614,036 alleles · common exomes 210,679/1,461,784 · genomes 26,062/152,252 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	25.6%	4
Ashkenazi Jewishnot grpmax-eligible	23.8%	4
Amishnot grpmax-eligible	15.7%	6
Admixed American	15.3%	7
Middle Eastern	15%	7
Remaining individualsnot grpmax-eligible	14.8%	7
European (non-Finnish)	14.7%	7
Finnishnot grpmax-eligible	12.5%	8
East Asian	8.7%	11
South Asian	6.02%	17

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.Ala830=
Coding: c.2490C>T
MANE Select: NM_001171
dbSNP: rs9924755
Type: single nucleotide variant
Location: chr16:16177552 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.32 · 4 PDB
Residue 830: a β-strand; the abc transporter 1 domain

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

Also linked: pseudoxanthoma elasticum, forme fruste arterial calcification, generalized, of infancy, 2

For Pseudoxanthoma elasticum (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

ABCC6 p.Ala830Pro Uncertain significance same residue
ABCC6 p.Ala830Thr 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

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-ala830 (accessed [today's date]).

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