Is ABCC6 p.Arg600Cys (c.1798C>T) pathogenic?

ABCC6 p.Arg600Cys (c.1798C>T) is classified Pathogenic/Likely pathogenic in ABCC6 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-24). AlphaMissense: ambiguous (0.4285); Very rare (popmax 0.00801%, afr); Associated with arterial calcification, generalized, of infancy, 2.

What condition is associated with ABCC6 p.Arg600Cys (c.1798C>T)?

ABCC6 p.Arg600Cys (c.1798C>T) is associated with arterial calcification, generalized, of infancy, 2, pseudoxanthoma elasticum, forme fruste, autosomal recessive inherited pseudoxanthoma elasticum (ClinVar).

How common is ABCC6 p.Arg600Cys (c.1798C>T) in the general population?

ABCC6 p.Arg600Cys (c.1798C>T) is very rare (popmax 0.00801%, afr) (gnomAD).

How is Generalized arterial calcification of infancy inherited?

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

What do computational predictors say about ABCC6 p.Arg600Cys (c.1798C>T)?

AlphaMissense predicts ambiguous (score 0.4285) — an in-silico prediction, not a clinical call.

ABCC6 p.Arg600Cys

c.1798C>T · rs72653777 · VCV433243

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.4285 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

arterial calcification, generalized, of infancy, 2

Computational evidence

Protein change
AlphaMissense	0.4285	ambiguous
REVEL	0.958	strongly pathogenic-leaning
SaProt	LLR -13.08	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 1.4, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 59 kb · p 0.39 · regional, not allelic
Overall
CADD	34.0	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

Grpmax group 0.00801% African / African-American · 6/74,896 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.00223% 36/1,613,516 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,483
Finnishnot grpmax-eligible	0.00313%	31,957
East Asian	0.00223%	44,880
European (non-Finnish)	0.00212%	47,193
Remaining individualsnot grpmax-eligible	0.0016%	62,454
South Asian	0.0011%	91,014

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.Arg600Cys
Coding: c.1798C>T
MANE Select: NM_001171
dbSNP: rs72653777
Type: single nucleotide variant
Location: chr16:16187193 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.32 · 4 PDB
Residue 600: a UniProt-annotated variant site (in pxe)

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

Disease context

arterial calcification, generalized, of infancy, 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pseudoxanthoma elasticum, forme fruste autosomal recessive inherited pseudoxanthoma elasticum

For Generalized arterial calcification of infancy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Antenatal, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Worldwide)

Similar variants

ABCC6 p.Arg600Leu Uncertain significance ⚠ same residue
ABCC6 p.Arg600Pro Pathogenic ★ same residue
ABCC6 p.Arg600His Conflicting classifications of pathogenicity ★ ⚠ 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-arg600cys (accessed [today's date]).

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