Is ACAN p.Arg2385Gln (c.7154G>A) pathogenic?

ACAN p.Arg2385Gln (c.7154G>A) is classified Uncertain significance in ACAN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-28). AlphaMissense: likely benign (0.1543); Ultra-rare (popmax 0.0658%, mid); Associated with Inborn genetic diseases.

What condition is associated with ACAN p.Arg2385Gln (c.7154G>A)?

ACAN p.Arg2385Gln (c.7154G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ACAN p.Arg2385Gln (c.7154G>A) in the general population?

ACAN p.Arg2385Gln (c.7154G>A) is ultra-rare (popmax 0.0658%, mid) (gnomAD).

What do computational predictors say about ACAN p.Arg2385Gln (c.7154G>A)?

AlphaMissense predicts likely benign (score 0.1543) — an in-silico prediction, not a clinical call.

ACAN p.Arg2385Gln

c.7154G>A · rs747182944 · VCV2887944

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1543 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0658%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1543	likely benign
REVEL	0.066	moderately benign-leaning
SaProt	LLR -7.05	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP -0.46, phastCons 0.73
Regional constraint	o/e 1.02	unconstrained · MANE · 18 kb · p 0.49 · regional, not allelic
Overall
CADD	16.99	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R2347Q vs ClinVar R2385Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0658% Middle Eastern · 4/6,078 alleles

Filtering AF 0.0224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0135%

Overall 0.00465% 75/1,613,740 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0658%	1,520
Remaining individualsnot grpmax-eligible	0.0112%	8,921
Admixed American	0.00833%	12,000
South Asian	0.00659%	15,179
Finnishnot grpmax-eligible	0.00626%	15,984
African / African-American	0.00534%	18,735
European (non-Finnish)	0.00373%	26,815
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,600

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.Arg2385Gln
Coding: c.7154G>A
MANE Select: NM_001369268
dbSNP: rs747182944
Type: single nucleotide variant
Location: chr15:88871475 (GRCh38)
Gene constraint: LOEUF 0.377 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 53.32 · 4 PDB
Residue 2385: a disulfide bond; the c-type lectin domain; the 'g3' region; a binding site

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ACAN p.Arg2385Trp Uncertain significance ★★ ⚠ same residue
ACAN p.Leu1606Ter Pathogenic/Likely pathogenic ★★ same condition
ACAN p.Ala1404Ser Uncertain significance ★★ ⚠ same condition
ACAN p.Ala2105Thr Uncertain significance ★★ ⚠ same condition
ACAN p.Ala2163Thr Uncertain significance ★★ ⚠ same condition
ACAN p.Ala2191Ser Uncertain significance ★★ ⚠ same condition
ACAN p.Ala2278Asp Uncertain significance ★★ ⚠ same condition
ACAN p.Ala2409Gly 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-arg2385gln (accessed [today's date]).

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