Is COL9A1 p.Ser22Pro (c.64T>C) pathogenic?

COL9A1 p.Ser22Pro (c.64T>C) is classified Uncertain significance in COL9A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-10). AlphaMissense: likely benign (0.0831); Absent from gnomAD v4.1.

How common is COL9A1 p.Ser22Pro (c.64T>C) in the general population?

COL9A1 p.Ser22Pro (c.64T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COL9A1 p.Ser22Pro (c.64T>C)?

AlphaMissense predicts likely benign (score 0.0831) — an in-silico prediction, not a clinical call.

COL9A1 p.Ser22Pro

c.64T>C · rs765061853 · VCV1051504

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0831 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0831	likely benign
REVEL	0.693	pathogenic-leaning
SaProt	LLR -9.08	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.4	GERP 2.1, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 86 kb · p 0.33 · regional, not allelic
Overall
CADD	20.3	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: COL9A1
Protein: p.Ser22Pro
Coding: c.64T>C
MANE Select: NM_001851
dbSNP: rs765061853
Type: single nucleotide variant
Location: chr6:70302025 (GRCh38)
Gene constraint: LOEUF 0.889 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 62.72 · 5 PDB

Full COL9A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COL9A1 c.1665+2T>C Likely pathogenic ★★ same type
COL9A1 p.Arg471Ter Pathogenic/Likely pathogenic ★★ same type
COL9A1 p.Arg507Ter Pathogenic ★★ same type
COL9A1 p.Gln750Ter Pathogenic/Likely pathogenic ★★ same type
COL9A1 p.Glu374Ter Pathogenic/Likely pathogenic ★★ same type
COL9A1 p.Lys139Ter Pathogenic/Likely pathogenic ★★ same type
COL9A1 p.Ser351Ter Likely pathogenic ★★ same type
COL9A1 p.Trp5Ter Pathogenic/Likely 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/col9a1-p-ser22pro (accessed [today's date]).

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