Is ABCC6 p.Arg297fs (c.890_905del) pathogenic?

ABCC6 p.Arg297fs (c.890905del) is classified Likely pathogenic in ABCC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-03-27). Very rare (popmax 8.48e-05%, nfe).

How common is ABCC6 p.Arg297fs (c.890_905del) in the general population?

ABCC6 p.Arg297fs (c.890_905del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

ABCC6 p.Arg297fs

c.890_905del · rs2152283906 · VCV1323817

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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

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 8 of 31
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.6	GERP 1.5, phastCons 0.97
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

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) · 1/1,179,884 alleles

Overall 6.84e-05% 1/1,461,666 alleles · very rare

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.Arg297fs
Coding: c.890_905del
MANE Select: NM_001171
dbSNP: rs2152283906
Type: Deletion
Location: chr16:16203503 (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

Similar variants

ABCC6 p.Arg297Cys Uncertain significance ★ ⚠ same residue
ABCC6 p.Arg297His Conflicting classifications of pathogenicity ★ ⚠ same residue
ABCC6 c.2248-2_2248-1del Pathogenic ★★ same type
ABCC6 c.3506+2_3506+5del Pathogenic/Likely pathogenic ★★ same type
ABCC6 c.998+2_998+3del Pathogenic/Likely pathogenic ★★ same type
ABCC6 p.Ala667fs Pathogenic/Likely pathogenic ★★ same type
ABCC6 p.Arg473fs Pathogenic/Likely pathogenic ★★ same type
ABCC6 p.Asp1368fs Pathogenic ★★ same type

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-arg297fs (accessed [today's date]).

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