Is ACAN p.Pro2306fs (c.6917del) pathogenic?

ACAN p.Pro2306fs (c.6917del) is classified Pathogenic in ACAN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-10). Very rare (popmax 8.48e-05%, nfe).

How common is ACAN p.Pro2306fs (c.6917del) in the general population?

ACAN p.Pro2306fs (c.6917del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

ACAN p.Pro2306fs

c.6917del · VCV4761334

Pathogenic Single submitter

Classification

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 in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 13 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.5	GERP 1.6, phastCons 0.75

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) · 1/1,179,796 alleles

Overall 6.84e-05% 1/1,461,388 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: ACAN
Protein: p.Pro2306fs
Coding: c.6917del
MANE Select: NM_001369268
Type: Deletion
Location: chr15:88860405 (GRCh38)
Gene constraint: LOEUF 0.377 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 53.32 · 4 PDB
Residue 2306: a disulfide bond; the egf-like domain; the 'g3' region

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

Similar variants

ACAN p.Asn108fs Pathogenic/Likely pathogenic ★★ same type
ACAN p.Glu518fs Pathogenic ★★ same type
ACAN p.Gly391fs Pathogenic ★★ same type
ACAN p.Ser410fs Pathogenic ★★ same type
ACAN p.Ser509fs Pathogenic ★★ same type
ACAN p.Thr259fs Pathogenic/Likely pathogenic ★★ same type
ACAN p.Trp290fs Pathogenic ★★ same type
ACAN p.Gly946_Glu964del Uncertain significance ★★ 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/acan-p-pro2306fs (accessed [today's date]).

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