Is COL10A1 p.Pro477Arg (c.1430C>G) pathogenic?

COL10A1 p.Pro477Arg (c.1430C>G) is classified Uncertain significance in COL10A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-18). AlphaMissense: likely benign (0.1498); Very rare (popmax 0.000433%, nfe).

How common is COL10A1 p.Pro477Arg (c.1430C>G) in the general population?

COL10A1 p.Pro477Arg (c.1430C>G) is very rare (popmax 0.000433%, nfe) (gnomAD).

What do computational predictors say about COL10A1 p.Pro477Arg (c.1430C>G)?

AlphaMissense predicts likely benign (score 0.1498) — an in-silico prediction, not a clinical call.

COL10A1 p.Pro477Arg

c.1430C>G · rs751106978 · VCV2133499

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1498 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000433%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1498	likely benign
REVEL	0.698	pathogenic-leaning
SaProt	LLR -10.89	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 0.97, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 5,416 bp · p 0.14 · regional, not allelic
Overall
CADD	22.7	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

Grpmax group 0.000433% European (non-Finnish) · 5/1,154,438 alleles

Filtering AF 0.000127% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.2e-05%

Overall 0.000323% 5/1,547,934 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.Pro477Arg
Coding: c.1430C>G
MANE Select: NM_000493
dbSNP: rs751106978
Type: single nucleotide variant
Location: chr6:116120686 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 58.80 · 1 PDB
Residue 477: the 'disordered' region; the 'triple-helical region' region

Full COL10A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COL10A1 p.Arg71Ter Pathogenic/Likely pathogenic ★★ same type
COL10A1 p.Cys591Arg Likely pathogenic ★★ same type
COL10A1 p.Gln653Ter Pathogenic/Likely pathogenic ★★ same type
COL10A1 p.Gly18Arg Pathogenic/Likely pathogenic ★★ ⚠ same type
COL10A1 p.Gly18Glu Pathogenic/Likely pathogenic ★★ ⚠ same type
COL10A1 p.Ser671Pro Pathogenic/Likely pathogenic ★★ same type
COL10A1 p.Tyr597His Pathogenic/Likely pathogenic ★★ ⚠ same type
COL10A1 p.Tyr663Ter 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/col10a1-p-pro477arg (accessed [today's date]).

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