Is ACAN p.Arg93= (c.279C>T) pathogenic?

ACAN p.Arg93= (c.279C>T) is classified Likely benign in ACAN (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-23). Very rare (popmax 0.00833%, amr).

How common is ACAN p.Arg93= (c.279C>T) in the general population?

ACAN p.Arg93= (c.279C>T) is very rare (popmax 0.00833%, amr) (gnomAD).

ACAN p.Arg93=

c.279C>T · rs754145054 · VCV739429

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

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 -3.5	GERP -3.5
Overall
CADD	5.138	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00833% Admixed American · 5/60,012 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.00112% 18/1,613,932 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	12,002
East Asian	0.00445%	22,447
African / African-American	0.00133%	74,938
European (non-Finnish)	0.000848%	117,991

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.Arg93=
Coding: c.279C>T
MANE Select: NM_001369268
dbSNP: rs754145054
Type: single nucleotide variant
Location: chr15:88838871 (GRCh38)
Gene constraint: LOEUF 0.377 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 53.32 · 4 PDB
Residue 93: 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

Similar variants

ACAN p.Arg93Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
ACAN p.Arg93His Uncertain significance ★ ⚠ same residue
ACAN p.Arg93fs Pathogenic 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

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-arg93 (accessed [today's date]).

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