Is COL10A1 p.Ser671Pro (c.2011T>C) pathogenic?

COL10A1 p.Ser671Pro (c.2011T>C) is classified Pathogenic/Likely pathogenic in COL10A1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-20). AlphaMissense: likely pathogenic (0.9783); Absent from gnomAD v4.1; Associated with Schmid metaphyseal chondrodysplasia.

What condition is associated with COL10A1 p.Ser671Pro (c.2011T>C)?

COL10A1 p.Ser671Pro (c.2011T>C) is associated with Schmid metaphyseal chondrodysplasia (ClinVar).

How common is COL10A1 p.Ser671Pro (c.2011T>C) in the general population?

COL10A1 p.Ser671Pro (c.2011T>C) is absent from gnomAD v4.1 (gnomAD).

How is Metaphyseal chondrodysplasia, Schmid type inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about COL10A1 p.Ser671Pro (c.2011T>C)?

AlphaMissense predicts likely pathogenic (score 0.9783) — an in-silico prediction, not a clinical call.

COL10A1 p.Ser671Pro

c.2011T>C · rs111033552 · VCV17477

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9783 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Schmid metaphyseal chondrodysplasia

Computational evidence

Protein change
AlphaMissense	0.9783	likely pathogenic ✓ concordant with ClinVar · top 1% in COL10A1
REVEL	0.737	pathogenic-leaning
SaProt	LLR -14.12	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.2	GERP 0.69, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 5,416 bp · p 0.14 · regional, not allelic
Overall
CADD	23.9	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: COL10A1
Protein: p.Ser671Pro
Coding: c.2011T>C
MANE Select: NM_000493
dbSNP: rs111033552
Type: single nucleotide variant
Location: chr6:116120105 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 58.80 · 1 PDB
Residue 671: the c1q domain; a UniProt-annotated variant site (in smcd); a β-strand; the 'nonhelical region (nc1)' region

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

Disease context

Schmid metaphyseal chondrodysplasia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Metaphyseal chondrodysplasia, Schmid type (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood, Infancy, Neonatal

Similar variants

COL10A1 p.Arg71Ter Pathogenic/Likely pathogenic ★★ same condition
COL10A1 p.Cys591Arg Likely pathogenic ★★ same condition
COL10A1 p.Gln653Ter Pathogenic/Likely pathogenic ★★ same condition
COL10A1 p.Gly18Arg Pathogenic/Likely pathogenic ★★ ⚠ same condition
COL10A1 p.Gly18Glu Pathogenic/Likely pathogenic ★★ ⚠ same condition
COL10A1 p.Tyr597His Pathogenic/Likely pathogenic ★★ ⚠ same condition
COL10A1 p.Tyr663Ter Pathogenic ★★ same condition
COL10A1 p.Ala328Thr 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-ser671pro (accessed [today's date]).

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