Is CCDC22 p.Ala462= (c.1386G>A) pathogenic?

CCDC22 p.Ala462= (c.1386G>A) is classified Likely benign in CCDC22 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-01). Ultra-rare (popmax 0.0176%, afr).

How common is CCDC22 p.Ala462= (c.1386G>A) in the general population?

CCDC22 p.Ala462= (c.1386G>A) is ultra-rare (popmax 0.0176%, afr) (gnomAD).

CCDC22 p.Ala462=

c.1386G>A · VCV3898311

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0176%, afr)

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 -0.29	GERP -3.4
Overall
CADD	1.173	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0176% African / African-American · 10/56,958 alleles

Filtering AF 0.00945% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00724%

Overall 0.00165% 20/1,208,841 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0176%	5,696
European (non-Finnish)	0.00112%	89,482

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.Ala462=
Coding: c.1386G>A
MANE Select: NM_014008
Type: single nucleotide variant
Location: chrX:49248689 (GRCh38)
Structure: AlphaFold pLDDT 78.95 · 4 PDB

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

Similar variants

CCDC22 p.Ala462Val Uncertain significance ★ ⚠ 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-ala462 (accessed [today's date]).

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