Is ABCC6 p.Thr630= (c.1890C>G) pathogenic?

ABCC6 p.Thr630= (c.1890C>G) is classified Benign in ABCC6 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). Common (popmax 50.1%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with pseudoxanthoma elasticum, forme fruste.

What condition is associated with ABCC6 p.Thr630= (c.1890C>G)?

ABCC6 p.Thr630= (c.1890C>G) is associated with pseudoxanthoma elasticum, forme fruste, autosomal recessive inherited pseudoxanthoma elasticum, arterial calcification, generalized, of infancy, 2 (ClinVar).

ABCC6 p.Thr630=

Q: How common is ABCC6 p.Thr630= (c.1890C>G) in the general population?

ABCC6 p.Thr630= (c.1890C>G) is common (popmax 50.1%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1890C>G · rs8058696 · VCV433246

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 50.1%, nfe) — 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 -5.9	GERP -3
Overall
CADD	0.118	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 50.1% European (non-Finnish) · 588,885/1,175,140 alleles

Filtering AF 50% ClinGen BA1/BS1 input FAF95, joint · FAF99 50%

Overall 46.4% 745,917/1,608,362 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	51.6%	2
European (non-Finnish)grpmax	50.1%	2
Admixed American	46.1%	2
Finnishnot grpmax-eligible	45.1%	2
Remaining individualsnot grpmax-eligible	43.6%	2
Ashkenazi Jewishnot grpmax-eligible	42.8%	2
Middle Eastern	35.4%	3
African / African-American	35.2%	3
South Asian	26%	4
East Asian	18.3%	5

Amish 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.Thr630=
Coding: c.1890C>G
MANE Select: NM_001171
dbSNP: rs8058696
Type: single nucleotide variant
Location: chr16:16185012 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.32 · 4 PDB
Residue 630: a β-strand; the abc transporter 1 domain

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 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
ABCC6 c.4209-2A>C 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-thr630 (accessed [today's date]).

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