Is ACAN p.Ala190Val (c.569C>T) pathogenic?

ACAN p.Ala190Val (c.569C>T) is classified Uncertain significance in ACAN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-11). AlphaMissense: ambiguous (0.5155); Absent from gnomAD v4.1.

How common is ACAN p.Ala190Val (c.569C>T) in the general population?

ACAN p.Ala190Val (c.569C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACAN p.Ala190Val (c.569C>T)?

AlphaMissense predicts ambiguous (score 0.5155) — an in-silico prediction, not a clinical call.

ACAN p.Ala190Val

c.569C>T · rs2505230955 · VCV2985774

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5155 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,605,774)

Computational evidence

Protein change
AlphaMissense	0.5155	ambiguous
REVEL	0.44	indeterminate
SaProt	LLR -9.26	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 19 kb · p 0.97 · regional, not allelic
Overall
CADD	24.6	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

No allele count reported in gnomAD v4.1 (AN 1,605,774). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ACAN
Protein: p.Ala190Val
Coding: c.569C>T
MANE Select: NM_001369268
dbSNP: rs2505230955
Type: single nucleotide variant
Location: chr15:88840126 (GRCh38)
Gene constraint: LOEUF 0.377 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 53.32 · 4 PDB
Residue 190: a disulfide bond; an α-helix; the link 1 domain; the 'g1-b' region

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

Similar variants

ACAN p.Ala190Thr Uncertain significance ★★ ⚠ same residue
ACAN p.Ala190= Likely benign ★ 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-ala190val (accessed [today's date]).

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