Is ABCC6 p.Asp1326= (c.3978C>T) pathogenic?

ABCC6 p.Asp1326= (c.3978C>T) is classified Benign/Likely benign in ABCC6 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-26). Rare (popmax 0.21%, afr); Associated with Inborn genetic diseases.

What condition is associated with ABCC6 p.Asp1326= (c.3978C>T)?

ABCC6 p.Asp1326= (c.3978C>T) is associated with Inborn genetic diseases, autosomal recessive inherited pseudoxanthoma elasticum (ClinVar).

How common is ABCC6 p.Asp1326= (c.3978C>T) in the general population?

ABCC6 p.Asp1326= (c.3978C>T) is rare (popmax 0.21%, afr) (gnomAD).

ABCC6 p.Asp1326=

c.3978C>T · rs57499803 · VCV433340

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.21%, afr)

Conditions

Inborn genetic diseases

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 -3.3	GERP -3.4
Overall
CADD	2.281	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.21% African / African-American · 157/74,670 alleles

Filtering AF 0.183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.173%

Overall 0.0214% 342/1,600,416 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.21%	476
Admixed American	0.036%	2,774
Remaining individualsnot grpmax-eligible	0.0258%	3,877
Middle Eastern	0.0166%	6,040
European (non-Finnish)	0.0123%	8,151
South Asian	0.00338%	29,553

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.Asp1326=
Coding: c.3978C>T
MANE Select: NM_001171
dbSNP: rs57499803
Type: single nucleotide variant
Location: chr16:16154936 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.32 · 4 PDB
Residue 1326: the abc transporter 2 domain

Full ABCC6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive inherited pseudoxanthoma elasticum

Similar variants

ABCC6 p.Asp1326Gly Uncertain significance ★★ ⚠ same residue
ABCC6 p.Asp1326Tyr Uncertain significance ★ ⚠ same residue
ABCC6 p.Asp1326Asn 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-asp1326 (accessed [today's date]).

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