Is ACAN p.Pro847= (c.2541C>T) pathogenic?

ACAN p.Pro847= (c.2541C>T) is classified Likely benign in ACAN (ClinVar, Single submitter, 3 submitters; last evaluated 2025-05-01). Rare (popmax 0.243%, nfe).

How common is ACAN p.Pro847= (c.2541C>T) in the general population?

ACAN p.Pro847= (c.2541C>T) is rare (popmax 0.243%, nfe) (gnomAD).

ACAN p.Pro847=

c.2541C>T · rs201758384 · VCV1328306

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.243%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.5	GERP -3.2
Overall
CADD	0.221	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.243% European (non-Finnish) · 2,863/1,176,460 alleles

Filtering AF 0.236% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.233%

Overall 0.252% 4,048/1,607,588 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.58%	63
European (non-Finnish)grpmax	0.243%	411
Remaining individualsnot grpmax-eligible	0.142%	706
South Asian	0.0499%	2,003
Admixed American	0.0319%	3,130
African / African-American	0.028%	3,567
Ashkenazi Jewishnot grpmax-eligible	0.00686%	14,583
East Asian	0.00447%	22,391

Finnish 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: ACAN
Protein: p.Pro847=
Coding: c.2541C>T
MANE Select: NM_001369268
dbSNP: rs201758384
Type: single nucleotide variant
Location: chr15:88855126 (GRCh38)
Gene constraint: LOEUF 0.377 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 53.32 · 4 PDB
Residue 847: the 'ks' region; the 'disordered' region

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

Similar variants

ACAN p.Pro847Ala Uncertain significance ★ ⚠ same residue
ACAN c.1733-2A>G Likely pathogenic ★★ same type
ACAN c.630-13G>A Pathogenic ★★ same type
ACAN c.7302+1G>A Pathogenic/Likely pathogenic ★★ same type
ACAN p.Arg236Ter Pathogenic ★★ same type
ACAN p.Arg386Ter Pathogenic/Likely pathogenic ★★ same type
ACAN p.Arg394Ter Pathogenic ★★ same type
ACAN p.Arg675Ter Pathogenic/Likely 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/acan-p-pro847 (accessed [today's date]).

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