Is ABCC6 p.Ser1229Asn (c.3686G>A) pathogenic?

ABCC6 p.Ser1229Asn (c.3686G>A) is classified Uncertain significance in ABCC6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-04-20). AlphaMissense: likely benign (0.1315); Absent from gnomAD v4.1; Associated with autosomal recessive inherited pseudoxanthoma elasticum.

What condition is associated with ABCC6 p.Ser1229Asn (c.3686G>A)?

ABCC6 p.Ser1229Asn (c.3686G>A) is associated with autosomal recessive inherited pseudoxanthoma elasticum, pseudoxanthoma elasticum, forme fruste, arterial calcification, generalized, of infancy, 2 (ClinVar).

How common is ABCC6 p.Ser1229Asn (c.3686G>A) in the general population?

ABCC6 p.Ser1229Asn (c.3686G>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.Ser1229Asn (c.3686G>A)?

AlphaMissense predicts likely benign (score 0.1315) — an in-silico prediction, not a clinical call.

ABCC6 p.Ser1229Asn

c.3686G>A · rs940876455 · VCV1348231

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1315 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal recessive inherited pseudoxanthoma elasticum

Computational evidence

Protein change
AlphaMissense	0.1315	likely benign
REVEL	0.247	benign-leaning
SaProt	LLR -6.14	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP 0.18, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 59 kb · p 0.39 · regional, not allelic
Overall
CADD	17.09	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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.Ser1229Asn
Coding: c.3686G>A
MANE Select: NM_001171
dbSNP: rs940876455
Type: single nucleotide variant
Location: chr16:16159531 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.32 · 4 PDB

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

Also linked: pseudoxanthoma elasticum, forme fruste arterial calcification, generalized, of infancy, 2

For Pseudoxanthoma elasticum (Orphanet):

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

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-ser1229asn (accessed [today's date]).

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