Is ACAN p.Arg95Trp (c.283C>T) pathogenic?

ACAN p.Arg95Trp (c.283C>T) is classified Uncertain significance in ACAN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-12). AlphaMissense: likely benign (0.2823); Very rare (popmax 0.00534%, afr); Associated with Inborn genetic diseases.

What condition is associated with ACAN p.Arg95Trp (c.283C>T)?

ACAN p.Arg95Trp (c.283C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ACAN p.Arg95Trp (c.283C>T) in the general population?

ACAN p.Arg95Trp (c.283C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about ACAN p.Arg95Trp (c.283C>T)?

AlphaMissense predicts likely benign (score 0.2823) — an in-silico prediction, not a clinical call.

ACAN p.Arg95Trp

c.283C>T · rs767131816 · VCV2180957

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2823 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2823	likely benign
REVEL	0.4	indeterminate
SaProt	LLR -14.21	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.43	GERP -2, phastCons 0.99
Regional constraint	o/e 1.00	unconstrained · MANE · 19 kb · p 0.97 · regional, not allelic
Overall
CADD	22.3	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,934 alleles

Filtering AF 0.002% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00176%

Overall 0.00254% 41/1,613,928 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,734
Remaining individualsnot grpmax-eligible	0.0048%	20,822
European (non-Finnish)	0.0028%	35,755
Admixed American	0.00167%	60,010

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.Arg95Trp
Coding: c.283C>T
MANE Select: NM_001369268
dbSNP: rs767131816
Type: single nucleotide variant
Location: chr15:88838875 (GRCh38)
Gene constraint: LOEUF 0.377 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 53.32 · 4 PDB
Residue 95: a disulfide bond; an α-helix; the ig-like v-type domain; the 'g1-a' region

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.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
ACAN p.Ala299Thr 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-arg95trp (accessed [today's date]).

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