Is COL10A1 p.Glu658Ter (c.1972G>T) pathogenic?

COL10A1 p.Glu658Ter (c.1972G>T) is classified Uncertain significance in COL10A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-27). Absent from gnomAD v4.1; Associated with Schmid metaphyseal chondrodysplasia.

What condition is associated with COL10A1 p.Glu658Ter (c.1972G>T)?

COL10A1 p.Glu658Ter (c.1972G>T) is associated with Schmid metaphyseal chondrodysplasia (ClinVar).

How common is COL10A1 p.Glu658Ter (c.1972G>T) in the general population?

COL10A1 p.Glu658Ter (c.1972G>T) 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.

COL10A1 p.Glu658Ter

c.1972G>T · VCV4855424

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Schmid metaphyseal chondrodysplasia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (3 of 3) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.1, phastCons 1
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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.Glu658Ter
Coding: c.1972G>T
MANE Select: NM_000493
Type: single nucleotide variant
Location: chr6:116120144 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 58.80 · 1 PDB
Residue 658: the c1q domain; 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.Glu658= Likely benign ★ same residue
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.Ser671Pro Pathogenic/Likely pathogenic ★★ same condition
COL10A1 p.Tyr597His Pathogenic/Likely pathogenic ★★ ⚠ 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-glu658ter (accessed [today's date]).

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