Is CCDC22 p.Arg346= (c.1038C>T) pathogenic?

CCDC22 p.Arg346= (c.1038C>T) is classified Likely benign in CCDC22 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-02-01). Ultra-rare (popmax 0.0237%, eas).

How common is CCDC22 p.Arg346= (c.1038C>T) in the general population?

CCDC22 p.Arg346= (c.1038C>T) is ultra-rare (popmax 0.0237%, eas) (gnomAD).

CCDC22 p.Arg346=

c.1038C>T · rs200287443 · VCV735112

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0237%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.1	GERP -3
Overall
CADD	7.149	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0237% East Asian · 8/33,718 alleles

Filtering AF 0.0118% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00852%

Overall 0.000745% 9/1,207,897 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0237%	4,215
African / African-American	0.00174%	57,348

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: CCDC22
Protein: p.Arg346=
Coding: c.1038C>T
MANE Select: NM_014008
dbSNP: rs200287443
Type: single nucleotide variant
Location: chrX:49247714 (GRCh38)
Structure: AlphaFold pLDDT 78.95 · 4 PDB
Residue 346: 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.Arg346Cys Uncertain significance ★ ⚠ same residue
CCDC22 p.Arg346His Conflicting classifications of pathogenicity ★ ⚠ same residue
CCDC22 p.Arg346Gly 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

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-arg346 (accessed [today's date]).

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