Is ABCC6 p.Tyr1069= (c.3207C>T) pathogenic?

ABCC6 p.Tyr1069= (c.3207C>T) is classified Benign/Likely benign in ABCC6 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-04-01). Rare (popmax 0.854%, nfe); Associated with pseudoxanthoma elasticum, forme fruste.

What condition is associated with ABCC6 p.Tyr1069= (c.3207C>T)?

ABCC6 p.Tyr1069= (c.3207C>T) is associated with pseudoxanthoma elasticum, forme fruste, autosomal recessive inherited pseudoxanthoma elasticum, arterial calcification, generalized, of infancy, 2 (ClinVar).

How common is ABCC6 p.Tyr1069= (c.3207C>T) in the general population?

ABCC6 p.Tyr1069= (c.3207C>T) is rare (popmax 0.854%, nfe) (gnomAD).

ABCC6 p.Tyr1069=

c.3207C>T · rs60975032 · VCV775105

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.854%, nfe)

Conditions

pseudoxanthoma elasticum, forme fruste

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.41 · evaluated, not missing
Constraint at this position
Conservation	phyloP -4.9	GERP -3.7
Overall
CADD	0.309	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.854% European (non-Finnish) · 10,083/1,180,024 alleles

Filtering AF 0.84% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.835%

Overall 0.687% 11,086/1,613,670 alleles · rare exomes 10,354/1,461,326 · genomes 732/152,344 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.854%	117
Remaining individualsnot grpmax-eligible	0.48%	208
Middle Eastern	0.396%	253
Finnishnot grpmax-eligible	0.395%	253
Amishnot grpmax-eligible	0.329%	304
Admixed American	0.277%	362
Ashkenazi Jewishnot grpmax-eligible	0.189%	529
African / African-American	0.163%	615
South Asian	0.0856%	1,168
East Asian	0.00668%	14,959

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.Tyr1069=
Coding: c.3207C>T
MANE Select: NM_001171
dbSNP: rs60975032
Type: single nucleotide variant
Location: chr16:16165722 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.32 · 4 PDB
Residue 1069: the abc transmembrane type-1 2 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 p.Tyr1069Asp Uncertain significance ★ ⚠ same residue
ABCC6 p.Tyr1069Ter Likely pathogenic 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-tyr1069 (accessed [today's date]).

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