Is ABCC6 p.Ser620fs (c.1857dup) pathogenic?

ABCC6 p.Ser620fs (c.1857dup) is classified Pathogenic/Likely pathogenic in ABCC6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-20). Very rare (popmax 8.48e-05%, nfe); Associated with autosomal recessive inherited pseudoxanthoma elasticum.

What condition is associated with ABCC6 p.Ser620fs (c.1857dup)?

ABCC6 p.Ser620fs (c.1857dup) is associated with autosomal recessive inherited pseudoxanthoma elasticum (ClinVar).

How common is ABCC6 p.Ser620fs (c.1857dup) in the general population?

ABCC6 p.Ser620fs (c.1857dup) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

How is Pseudoxanthoma elasticum inherited?

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

ABCC6 p.Ser620fs

c.1857dup · rs72664218 · VCV433245

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

autosomal recessive inherited pseudoxanthoma elasticum

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 14 of 31
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.3	GERP -0.75, phastCons 0.64

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,288 alleles

Overall 0.000137% 2/1,460,780 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,448
European (non-Finnish)grpmax	8.48e-05%	1,179,288

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser620fs
Coding: c.1857dup
MANE Select: NM_001171
dbSNP: rs72664218
Type: Duplication
Location: chr16:16187133 (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

For Pseudoxanthoma elasticum (Orphanet):

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

Similar variants

ABCC6 p.Ile1330fs Pathogenic/Likely pathogenic ★★ same condition
ABCC6 p.Ser66fs Pathogenic ★★ same condition
ABCC6 p.Trp1259fs Pathogenic ★★ same condition
ABCC6 c.1636-3dup Uncertain significance ★ same condition
ABCC6 p.Thr603fs Conflicting classifications of pathogenicity ★ same condition
ABCC6 p.Ala1291fs Likely pathogenic same condition
ABCC6 p.Arg526fs Likely pathogenic same condition
ABCC6 p.Glu1277delinsLysIleProThrTer 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-ser620fs (accessed [today's date]).

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