Is CCDC22 p.Gln324His (c.972G>C) pathogenic?

CCDC22 p.Gln324His (c.972G>C) is classified Likely benign in CCDC22 (ClinVar, Single submitter, 2 submitters; last evaluated 2018-02-21). AlphaMissense: likely benign (0.1718); Very rare (popmax 0.000113%, nfe).

How common is CCDC22 p.Gln324His (c.972G>C) in the general population?

CCDC22 p.Gln324His (c.972G>C) is very rare (popmax 0.000113%, nfe) (gnomAD).

What do computational predictors say about CCDC22 p.Gln324His (c.972G>C)?

AlphaMissense predicts likely benign (score 0.1718) — an in-silico prediction, not a clinical call.

CCDC22 p.Gln324His

c.972G>C · rs587780297 · VCV128628

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1718 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000113%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1718	likely benign
REVEL	0.115	moderately benign-leaning
SaProt	LLR -7.24	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.26	donor loss · deltas
Pangolin	Δ0.52	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 5,832 bp · p 0.85 · regional, not allelic
Overall
CADD	29.3	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

Grpmax group 0.000113% European (non-Finnish) · 1/888,166 alleles

Overall 0.000888% 1/112,648 alleles · very rare

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.Gln324His
Coding: c.972G>C
MANE Select: NM_014008
dbSNP: rs587780297
Type: single nucleotide variant
Location: chrX:49247558 (GRCh38)
Structure: AlphaFold pLDDT 78.95 · 4 PDB
Residue 324: 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.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-gln324his (accessed [today's date]).

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