Is ABCC6 p.Ala766Asp (c.2297C>A) pathogenic?

ABCC6 p.Ala766Asp (c.2297C>A) is classified Pathogenic in ABCC6 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-03-01). AlphaMissense: likely pathogenic (0.9446); Absent from gnomAD v4.1; Associated with autosomal recessive inherited pseudoxanthoma elasticum.

What condition is associated with ABCC6 p.Ala766Asp (c.2297C>A)?

ABCC6 p.Ala766Asp (c.2297C>A) is associated with autosomal recessive inherited pseudoxanthoma elasticum (ClinVar).

How common is ABCC6 p.Ala766Asp (c.2297C>A) in the general population?

ABCC6 p.Ala766Asp (c.2297C>A) is absent from gnomAD v4.1 (gnomAD).

How is Pseudoxanthoma elasticum inherited?

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

What do computational predictors say about ABCC6 p.Ala766Asp (c.2297C>A)?

AlphaMissense predicts likely pathogenic (score 0.9446) — an in-silico prediction, not a clinical call.

ABCC6 p.Ala766Asp

c.2297C>A · rs72653789 · VCV433269

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9446 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal recessive inherited pseudoxanthoma elasticum

Computational evidence

Protein change
AlphaMissense	0.9446	likely pathogenic ✓ concordant with ClinVar · top 1% in ABCC6
REVEL	0.985	strongly pathogenic-leaning
SaProt	LLR -15.77	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 59 kb · p 0.39 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABCC6
Protein: p.Ala766Asp
Coding: c.2297C>A
MANE Select: NM_001171
dbSNP: rs72653789
Type: single nucleotide variant
Location: chr16:16178916 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.32 · 4 PDB
Residue 766: a UniProt-annotated variant site (in pxe; affects protein expression and trafficking; expression is reduced to less than 10%, when compared with the wt protein); an α-helix; 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

For Pseudoxanthoma elasticum (Orphanet):

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

Similar variants

ABCC6 p.Ala766Val 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-ala766asp (accessed [today's date]).

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