Is COL22A1 p.Arg232Ser (c.694C>A) pathogenic?

COL22A1 p.Arg232Ser (c.694C>A) is classified Uncertain significance in COL22A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-03). AlphaMissense: ambiguous (0.4058); Absent from gnomAD v4.1.

How common is COL22A1 p.Arg232Ser (c.694C>A) in the general population?

COL22A1 p.Arg232Ser (c.694C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COL22A1 p.Arg232Ser (c.694C>A)?

AlphaMissense predicts ambiguous (score 0.4058) — an in-silico prediction, not a clinical call.

COL22A1 p.Arg232Ser

c.694C>A · VCV4655565

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4058 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4058	ambiguous
REVEL	0.546	indeterminate
SaProt	LLR 0.22	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP -0.41, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 294 kb · p 0.19 · regional, not allelic
Overall
CADD	23.9	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: COL22A1
Protein: p.Arg232Ser
Coding: c.694C>A
MANE Select: NM_152888
Type: single nucleotide variant
Location: chr8:138844123 (GRCh38)
Gene constraint: LOEUF 1.005 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.25

Full COL22A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COL22A1 p.Arg232Cys Uncertain significance ★ ⚠ same residue
COL22A1 p.Glu736Asp Benign ★★ same type
COL22A1 p.Gly1180= Benign ★★ same type
COL22A1 p.Pro763Leu Benign ★★ same type
COL22A1 p.Ala1005Ser Uncertain significance ★ ⚠ same type
COL22A1 p.Ala103Val Uncertain significance ★ ⚠ same type
COL22A1 p.Ala1077Gly Uncertain significance ★ ⚠ same type
COL22A1 p.Ala120Ser Uncertain significance ★ ⚠ 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/col22a1-p-arg232ser (accessed [today's date]).

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