Is CCDC22 p.Arg436Gly (c.1306C>G) pathogenic?

CCDC22 p.Arg436Gly (c.1306C>G) is classified Uncertain significance in CCDC22 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-05). AlphaMissense: ambiguous (0.4074); Absent from gnomAD v4.1.

How common is CCDC22 p.Arg436Gly (c.1306C>G) in the general population?

CCDC22 p.Arg436Gly (c.1306C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCDC22 p.Arg436Gly (c.1306C>G)?

AlphaMissense predicts ambiguous (score 0.4074) — an in-silico prediction, not a clinical call.

CCDC22 p.Arg436Gly

c.1306C>G · VCV3602948

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4074 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4074	ambiguous
REVEL	0.148	moderately benign-leaning
SaProt	LLR -9.92	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 1.6, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 5,832 bp · p 0.85 · regional, not allelic
Overall
CADD	22.6	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: CCDC22
Protein: p.Arg436Gly
Coding: c.1306C>G
MANE Select: NM_014008
Type: single nucleotide variant
Location: chrX:49248500 (GRCh38)
Structure: AlphaFold pLDDT 78.95 · 4 PDB
Residue 436: the 'sufficicient and required for interaction with ccdc93' region

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

Similar variants

CCDC22 p.Arg436Gln Likely benign ★ same residue
CCDC22 p.Ala463Gly Uncertain significance ★★ ⚠ same type
CCDC22 p.Arg107Cys Uncertain significance ★★ ⚠ same type
CCDC22 p.Arg128Gln Uncertain significance ★★ ⚠ same type
CCDC22 p.Arg135Gln Uncertain significance ★★ ⚠ same type
CCDC22 p.Arg148Cys Uncertain significance ★★ ⚠ same type
CCDC22 p.Arg245Gln Uncertain significance ★★ ⚠ same type
CCDC22 p.Arg257His 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/ccdc22-p-arg436gly (accessed [today's date]).

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