Is ACAN p.Arg386Ter (c.1156C>T) pathogenic?

ACAN p.Arg386Ter (c.1156C>T) is classified Pathogenic/Likely pathogenic in ACAN (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-05-22). Very rare (popmax 0.00167%, amr); Associated with ACAN-related disorder.

What condition is associated with ACAN p.Arg386Ter (c.1156C>T)?

ACAN p.Arg386Ter (c.1156C>T) is associated with ACAN-related disorder (ClinVar).

How common is ACAN p.Arg386Ter (c.1156C>T) in the general population?

ACAN p.Arg386Ter (c.1156C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

ACAN p.Arg386Ter

c.1156C>T · rs773948197 · VCV499582

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

ACAN-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 7 of 19
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.41	GERP -1.7
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,014 alleles

Overall 0.000657% 1/152,258 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.Arg386Ter
Coding: c.1156C>T
MANE Select: NM_001369268
dbSNP: rs773948197
Type: single nucleotide variant
Location: chr15:88845609 (GRCh38)
Gene constraint: LOEUF 0.377 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 53.32 · 4 PDB

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

Disease context

ACAN-related disorder

Similar variants

ACAN p.Arg386Gln Uncertain significance ★ ⚠ same residue
ACAN c.630-13G>A Pathogenic ★★ same condition
ACAN p.Arg236Ter Pathogenic ★★ same condition
ACAN p.Arg394Ter Pathogenic ★★ same condition
ACAN p.Cys2304Ter Pathogenic/Likely pathogenic ★★ same condition
ACAN p.Val2455Met Pathogenic/Likely pathogenic ★★ same condition
ACAN p.Ala171Val Uncertain significance ★★ ⚠ same condition
ACAN p.Ala248Thr Uncertain significance ★★ ⚠ 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/acan-p-arg386ter (accessed [today's date]).

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