Is COL10A1 p.Ser50Arg (c.150T>A) pathogenic?

COL10A1 p.Ser50Arg (c.150T>A) is classified Benign/Likely benign in COL10A1 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-05-21). AlphaMissense: likely benign (0.2182); Rare (popmax 0.763%, nfe); Associated with Schmid metaphyseal chondrodysplasia.

What condition is associated with COL10A1 p.Ser50Arg (c.150T>A)?

COL10A1 p.Ser50Arg (c.150T>A) is associated with Schmid metaphyseal chondrodysplasia (ClinVar).

How common is COL10A1 p.Ser50Arg (c.150T>A) in the general population?

COL10A1 p.Ser50Arg (c.150T>A) is rare (popmax 0.763%, nfe) (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.Ser50Arg (c.150T>A)?

AlphaMissense predicts likely benign (score 0.2182) — an in-silico prediction, not a clinical call.

COL10A1 p.Ser50Arg

c.150T>A · rs142411445 · VCV355113

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.2182 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.763%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Schmid metaphyseal chondrodysplasia

Computational evidence

Protein change
AlphaMissense	0.2182	likely benign
REVEL	0.279	benign-leaning
SaProt	LLR -6.88	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.5	GERP -2.1, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 5,416 bp · p 0.14 · regional, not allelic
Overall
CADD	19.56	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 0.763% European (non-Finnish) · 9,000/1,179,542 alleles

Filtering AF 0.75% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.744%

Overall 0.605% 9,758/1,613,252 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.763%	131
Remaining individualsnot grpmax-eligible	0.56%	178
Admixed American	0.3%	333
Finnishnot grpmax-eligible	0.178%	561
African / African-American	0.139%	721
Ashkenazi Jewishnot grpmax-eligible	0.0237%	4,223
Middle Eastern	0.0165%	6,054
East Asian	0.00223%	44,804
South Asian	0.0011%	90,990

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.Ser50Arg
Coding: c.150T>A
MANE Select: NM_152729 · reported on NM_000493
dbSNP: rs142411445
Type: single nucleotide variant
Location: chr6:116125343 (GRCh38)

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

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-ser50arg (accessed [today's date]).

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