Is ACAN p.Ala63Pro (c.187G>C) pathogenic?

ACAN p.Ala63Pro (c.187G>C) is classified Uncertain significance in ACAN (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-24). AlphaMissense: ambiguous (0.3601); Absent from gnomAD v4.1.

How common is ACAN p.Ala63Pro (c.187G>C) in the general population?

ACAN p.Ala63Pro (c.187G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACAN p.Ala63Pro (c.187G>C)?

AlphaMissense predicts ambiguous (score 0.3601) — an in-silico prediction, not a clinical call.

ACAN p.Ala63Pro

c.187G>C · rs749720584 · VCV1398387

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3601 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3601	ambiguous
REVEL	0.115	moderately benign-leaning
SaProt	LLR -6.26	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 19 kb · p 0.97 · regional, not allelic
Overall
CADD	23.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ACAN
Protein: p.Ala63Pro
Coding: c.187G>C
MANE Select: NM_001369268
dbSNP: rs749720584
Type: single nucleotide variant
Location: chr15:88838779 (GRCh38)
Gene constraint: LOEUF 0.377 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 53.32 · 4 PDB
Residue 63: 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.Ala63Asp Uncertain significance ★ ⚠ same residue
ACAN p.Ala63Thr 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

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-ala63pro (accessed [today's date]).

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