Is CCDC22 p.Pro172Arg (c.514_515delinsAG) pathogenic?

CCDC22 p.Pro172Arg (c.514515delinsAG) is classified Uncertain significance in CCDC22 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-01-27). Absent from gnomAD; Associated with Ritscher-Schinzel syndrome 2.

What condition is associated with CCDC22 p.Pro172Arg (c.514_515delinsAG)?

CCDC22 p.Pro172Arg (c.514_515delinsAG) is associated with Ritscher-Schinzel syndrome 2 (ClinVar).

How common is CCDC22 p.Pro172Arg (c.514_515delinsAG) in the general population?

CCDC22 p.Pro172Arg (c.514_515delinsAG) is absent from gnomAD (gnomAD).

CCDC22 p.Pro172Arg

c.514_515delinsAG · rs2065972358 · VCV995994

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Ritscher-Schinzel syndrome 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.6	GERP -0.74, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 5,832 bp · p 0.85 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CCDC22
Protein: p.Pro172Arg
Coding: c.514_515delinsAG
MANE Select: NM_014008
dbSNP: rs2065972358
Type: Indel
Location: chrX:49243163 (GRCh38)
Structure: AlphaFold pLDDT 78.95 · 4 PDB
Residue 172: the 'sufficicient and required for interaction with ccdc93' region; the 'sufficient for interaction with commd1' region

Full CCDC22 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Ritscher-Schinzel syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CCDC22 p.Ala463Gly Uncertain significance ★★ ⚠ same condition
CCDC22 p.Arg107Cys Uncertain significance ★★ ⚠ same condition
CCDC22 p.Arg128Gln Uncertain significance ★★ ⚠ same condition
CCDC22 p.Arg245Gln Uncertain significance ★★ ⚠ same condition
CCDC22 p.Arg623Trp Uncertain significance ★★ ⚠ same condition
CCDC22 p.Arg625Trp Uncertain significance ★★ ⚠ same condition
CCDC22 p.Arg66His Uncertain significance ★★ ⚠ same condition
CCDC22 p.Pro187Ser Uncertain significance ★★ ⚠ same condition

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/ccdc22-p-pro172arg (accessed [today's date]).

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