Is COL10A1 p.Pro196Ser (c.586C>T) pathogenic?

COL10A1 p.Pro196Ser (c.586C>T) is classified Uncertain significance in COL10A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-30). AlphaMissense: likely benign (0.0865); Very rare (popmax 0.00167%, amr).

How common is COL10A1 p.Pro196Ser (c.586C>T) in the general population?

COL10A1 p.Pro196Ser (c.586C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about COL10A1 p.Pro196Ser (c.586C>T)?

AlphaMissense predicts likely benign (score 0.0865) — an in-silico prediction, not a clinical call.

COL10A1 p.Pro196Ser

c.586C>T · VCV3625618

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0865 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0865	likely benign
REVEL	0.396	indeterminate
SaProt	LLR -11.15	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 5,416 bp · p 0.14 · regional, not allelic
Overall
CADD	24.4	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 0.00167% Admixed American · 1/60,022 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000479% 7/1,461,878 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,252
Admixed Americangrpmax	0.00167%	60,022
European (non-Finnish)	0.000339%	295,002

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro196Ser
Coding: c.586C>T
MANE Select: NM_000493
Type: single nucleotide variant
Location: chr6:116121530 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 58.80 · 1 PDB
Residue 196: 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-pro196ser (accessed [today's date]).

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