Is COL10A1 p.Pro509Arg (c.1526C>G) pathogenic?

COL10A1 p.Pro509Arg (c.1526C>G) is classified Uncertain significance in COL10A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-26). AlphaMissense: likely benign (0.1382); Very rare (popmax 0.00183%, amr); Associated with Inborn genetic diseases.

What condition is associated with COL10A1 p.Pro509Arg (c.1526C>G)?

COL10A1 p.Pro509Arg (c.1526C>G) is associated with Inborn genetic diseases (ClinVar).

How common is COL10A1 p.Pro509Arg (c.1526C>G) in the general population?

COL10A1 p.Pro509Arg (c.1526C>G) is very rare (popmax 0.00183%, amr) (gnomAD).

What do computational predictors say about COL10A1 p.Pro509Arg (c.1526C>G)?

AlphaMissense predicts likely benign (score 0.1382) — an in-silico prediction, not a clinical call.

COL10A1 p.Pro509Arg

c.1526C>G · VCV3834940

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1382 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00183%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1382	likely benign
REVEL	0.748	pathogenic-leaning
SaProt	LLR -9.89	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	GERP 1.1, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 5,416 bp · p 0.14 · regional, not allelic
Overall
CADD	21.5	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 0.00183% Admixed American · 1/54,712 alleles

Overall 6.97e-05% 1/1,435,334 alleles · very rare

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: COL10A1
Protein: p.Pro509Arg
Coding: c.1526C>G
MANE Select: NM_000493
Type: single nucleotide variant
Location: chr6:116120590 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 58.80 · 1 PDB
Residue 509: the 'disordered' region; the 'triple-helical region' region

Full COL10A1 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

COL10A1 p.Ala22Thr Uncertain significance ★★ ⚠ same condition
COL10A1 p.Ala328Thr Uncertain significance ★★ ⚠ same condition
COL10A1 p.Ala429Thr Uncertain significance ★★ ⚠ same condition
COL10A1 p.Ala439Ser Uncertain significance ★★ ⚠ same condition
COL10A1 p.Ala478Val Uncertain significance ★★ ⚠ same condition
COL10A1 p.Ala678Pro Uncertain significance ★★ ⚠ same condition
COL10A1 p.Arg170Gly Uncertain significance ★★ ⚠ same condition
COL10A1 p.Arg24Gln 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/col10a1-p-pro509arg (accessed [today's date]).

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