Is CCDC22 p.Gln249= (c.747A>G) pathogenic?

CCDC22 p.Gln249= (c.747A>G) is classified Benign in CCDC22 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). Common (popmax 72.2%, nfe) — too common for a highly-penetrant pathogenic allele.

CCDC22 p.Gln249=

Q: How common is CCDC22 p.Gln249= (c.747A>G) in the general population?

CCDC22 p.Gln249= (c.747A>G) is common (popmax 72.2%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.747A>G · rs2294020 · VCV769177

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 72.2%, nfe) — too common for a highly-penetrant pathogenic allele

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 0.72	GERP -2.1, phastCons 1
Overall
CADD	1.531	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 72.2% European (non-Finnish) · 631,702/875,376 alleles

Filtering AF 72% ClinGen BA1/BS1 input FAF95, joint · FAF99 72%

Overall 68.6% 802,774/1,171,060 alleles · common

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	78.5%	1
European (non-Finnish)grpmax	72.2%	1
Middle Eastern	71%	1
South Asian	69%	1
Remaining individualsnot grpmax-eligible	67%	1
Finnishnot grpmax-eligible	64.7%	2
Amishnot grpmax-eligible	62.4%	2
Admixed American	48.6%	2
African / African-American	43.9%	2
East Asian	39.6%	3

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Gln249=
Coding: c.747A>G
MANE Select: NM_014008
dbSNP: rs2294020
Type: single nucleotide variant
Location: chrX:49246763 (GRCh38)
Structure: AlphaFold pLDDT 78.95 · 4 PDB
Residue 249: the 'sufficicient and required for interaction with ccdc93' region; an α-helix; the 'sufficient for interaction with commd1' region

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

Similar variants

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
CCDC22 p.Arg379Cys 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-gln249 (accessed [today's date]).

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