Is CCDC22 p.Ala185Thr (c.553G>A) pathogenic?

CCDC22 p.Ala185Thr (c.553G>A) is classified Likely benign in CCDC22 (ClinVar, Single submitter, 3 submitters; last evaluated 2026-03-01). AlphaMissense: likely benign (0.0796); Ultra-rare (popmax 0.0232%, mid).

How common is CCDC22 p.Ala185Thr (c.553G>A) in the general population?

CCDC22 p.Ala185Thr (c.553G>A) is ultra-rare (popmax 0.0232%, mid) (gnomAD).

What do computational predictors say about CCDC22 p.Ala185Thr (c.553G>A)?

AlphaMissense predicts likely benign (score 0.0796) — an in-silico prediction, not a clinical call.

CCDC22 p.Ala185Thr

c.553G>A · rs782522722 · VCV1206362

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0796 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0232%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0796	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -7.00	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.5	GERP -0.8, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 5,832 bp · p 0.85 · regional, not allelic
Overall
CADD	19.5	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 0.0232% Middle Eastern · 1/4,304 alleles

Filtering AF 0.00249% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00217%

Overall 0.00386% 42/1,087,873 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0232%	4,304
Remaining individualsnot grpmax-eligible	0.0148%	6,745
Finnishnot grpmax-eligible	0.00648%	15,433
European (non-Finnish)	0.00348%	28,713

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.Ala185Thr
Coding: c.553G>A
MANE Select: NM_014008
dbSNP: rs782522722
Type: single nucleotide variant
Location: chrX:49243301 (GRCh38)
Structure: AlphaFold pLDDT 78.95 · 4 PDB
Residue 185: the 'sufficicient and required for interaction with ccdc93' region; 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-ala185thr (accessed [today's date]).

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