Is ACAN p.Pro929Ser (c.2785C>T) pathogenic?

ACAN p.Pro929Ser (c.2785C>T) is classified Likely benign in ACAN (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-01). AlphaMissense: likely benign (0.0841); Ultra-rare (popmax 0.0735%, eas); Associated with Inborn genetic diseases.

What condition is associated with ACAN p.Pro929Ser (c.2785C>T)?

ACAN p.Pro929Ser (c.2785C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ACAN p.Pro929Ser (c.2785C>T) in the general population?

ACAN p.Pro929Ser (c.2785C>T) is ultra-rare (popmax 0.0735%, eas) (gnomAD).

What do computational predictors say about ACAN p.Pro929Ser (c.2785C>T)?

AlphaMissense predicts likely benign (score 0.0841) — an in-silico prediction, not a clinical call.

ACAN p.Pro929Ser

c.2785C>T · rs546089499 · VCV2248106

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0841 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0735%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0841	likely benign
REVEL	0.025	moderately benign-leaning
SaProt	LLR -6.89	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 -0.83	GERP -1.9, phastCons 0.004
Regional constraint	o/e 1.00	unconstrained · MANE · 19 kb · p 0.97 · regional, not allelic
Overall
CADD	0.039	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 0.0735% East Asian · 33/44,868 alleles

Filtering AF 0.0538% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0471%

Overall 0.00211% 34/1,612,948 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0735%	1,360
European (non-Finnish)	8.48e-05%	1,179,220

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.Pro929Ser
Coding: c.2785C>T
MANE Select: NM_001369268
dbSNP: rs546089499
Type: single nucleotide variant
Location: chr15:88855370 (GRCh38)
Gene constraint: LOEUF 0.377 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 53.32 · 4 PDB
Residue 929: the 'disordered' region; the 'cs-1' 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-pro929ser (accessed [today's date]).

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