Is CCDC22 p.Leu429= (c.1287C>T) pathogenic?

CCDC22 p.Leu429= (c.1287C>T) is classified Likely benign in CCDC22 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-02). Ultra-rare (popmax 0.0526%, afr); Associated with CCDC22-related disorder.

What condition is associated with CCDC22 p.Leu429= (c.1287C>T)?

CCDC22 p.Leu429= (c.1287C>T) is associated with CCDC22-related disorder (ClinVar).

How common is CCDC22 p.Leu429= (c.1287C>T) in the general population?

CCDC22 p.Leu429= (c.1287C>T) is ultra-rare (popmax 0.0526%, afr) (gnomAD).

CCDC22 p.Leu429=

c.1287C>T · rs140806879 · VCV3037595

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0526%, afr)

Conditions

CCDC22-related disorder

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 -1.4	GERP -2.8
Overall
CADD	0.107	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0526% African / African-American · 30/57,059 alleles

Filtering AF 0.0378% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0328%

Overall 0.0058% 70/1,207,800 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0526%	1,902
South Asian	0.0265%	3,770
Remaining individualsnot grpmax-eligible	0.0126%	7,919
Admixed American	0.00219%	45,726
European (non-Finnish)	0.00201%	49,680

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.Leu429=
Coding: c.1287C>T
MANE Select: NM_014008
dbSNP: rs140806879
Type: single nucleotide variant
Location: chrX:49248481 (GRCh38)
Structure: AlphaFold pLDDT 78.95 · 4 PDB
Residue 429: the 'sufficicient and required for interaction with ccdc93' region

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

Disease context

CCDC22-related disorder

Similar variants

CCDC22 p.Gln569Glu Uncertain significance ★★ ⚠ same condition
CCDC22 p.Pro141Thr Uncertain significance ★ ⚠ same condition
CCDC22 p.Arg607Gln Uncertain significance ⚠ same condition
CCDC22 p.Gln364Pro Uncertain significance ⚠ same condition
CCDC22 p.Ser319Tyr Uncertain significance ⚠ same condition
CCDC22 c.51-9C>T Likely benign same condition
CCDC22 p.Arg607Trp Likely benign ⚠ same condition
CCDC22 p.Ala463Gly 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-leu429 (accessed [today's date]).

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