Is ABCC6 p.Ala524Pro (c.1570G>C) pathogenic?

ABCC6 p.Ala524Pro (c.1570G>C) is classified Uncertain significance in ABCC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-19). AlphaMissense: ambiguous (0.4542); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ABCC6 p.Ala524Pro (c.1570G>C)?

ABCC6 p.Ala524Pro (c.1570G>C) is associated with Inborn genetic diseases (ClinVar).

How common is ABCC6 p.Ala524Pro (c.1570G>C) in the general population?

ABCC6 p.Ala524Pro (c.1570G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCC6 p.Ala524Pro (c.1570G>C)?

AlphaMissense predicts ambiguous (score 0.4542) — an in-silico prediction, not a clinical call.

ABCC6 p.Ala524Pro

c.1570G>C · VCV4130054

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4542 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4542	ambiguous
REVEL	0.715	pathogenic-leaning
SaProt	LLR -8.80	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.4	GERP 1.5, phastCons 0.027
Regional constraint	o/e 0.98	unconstrained · MANE · 59 kb · p 0.39 · regional, not allelic
Overall
CADD	23.0	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.Ala524Pro
Coding: c.1570G>C
MANE Select: NM_001171
Type: single nucleotide variant
Location: chr16:16190229 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.32 · 4 PDB
Residue 524: the abc transmembrane type-1 1 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

Similar variants

ABCC6 p.Ala524Ser Uncertain significance ★★ ⚠ same residue
ABCC6 p.Ala524Thr Uncertain significance ★★ ⚠ same residue
ABCC6 p.Ala1008Val Uncertain significance ★★ ⚠ same condition
ABCC6 p.Ala101Gly Uncertain significance ★★ ⚠ same condition
ABCC6 p.Ala1370Thr Uncertain significance ★★ ⚠ same condition
ABCC6 p.Ala1385Val Uncertain significance ★★ ⚠ same condition
ABCC6 p.Ala263Gly Uncertain significance ★★ ⚠ same condition
ABCC6 p.Ala353Thr Uncertain significance ★★ ⚠ 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-ala524pro (accessed [today's date]).

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