Is COL10A1 p.Pro399Ser (c.1195C>T) pathogenic?

COL10A1 p.Pro399Ser (c.1195C>T) is classified Uncertain significance in COL10A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-26). AlphaMissense: likely benign (0.1011); Very rare (popmax 0.0011%, sas).

How common is COL10A1 p.Pro399Ser (c.1195C>T) in the general population?

COL10A1 p.Pro399Ser (c.1195C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about COL10A1 p.Pro399Ser (c.1195C>T)?

AlphaMissense predicts likely benign (score 0.1011) — an in-silico prediction, not a clinical call.

COL10A1 p.Pro399Ser

c.1195C>T · rs2534087848 · VCV1994003

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1011 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.1011	likely benign
REVEL	0.277	benign-leaning
SaProt	LLR -7.86	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5.2	GERP -2.1, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 5,416 bp · p 0.14 · regional, not allelic
Overall
CADD	15.94	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,066 alleles

Overall 6.2e-05% 1/1,613,910 alleles · very rare exomes 1/1,461,798 · genomes 0/152,112 · joint denominator

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.Pro399Ser
Coding: c.1195C>T
MANE Select: NM_000493
dbSNP: rs2534087848
Type: single nucleotide variant
Location: chr6:116120921 (GRCh38)

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

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-pro399ser (accessed [today's date]).

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