Is CCDC22 p.Arg202Ser (c.606G>T) pathogenic?

CCDC22 p.Arg202Ser (c.606G>T) is classified Uncertain significance in CCDC22 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-03). AlphaMissense: ambiguous (0.3509); Very rare (popmax 0.00213%, nfe).

How common is CCDC22 p.Arg202Ser (c.606G>T) in the general population?

CCDC22 p.Arg202Ser (c.606G>T) is very rare (popmax 0.00213%, nfe) (gnomAD).

What do computational predictors say about CCDC22 p.Arg202Ser (c.606G>T)?

AlphaMissense predicts ambiguous (score 0.3509) — an in-silico prediction, not a clinical call.

CCDC22 p.Arg202Ser

c.606G>T · VCV3486584

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3509 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00213%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3509	ambiguous
REVEL	0.156	moderately benign-leaning
SaProt	LLR -7.42	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP -0.77, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 5,832 bp · p 0.85 · regional, not allelic
Overall
CADD	13.68	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 0.00213% European (non-Finnish) · 19/891,467 alleles

Filtering AF 0.00136% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0011%

Overall 0.00183% 22/1,203,126 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00423%	23,660
European (non-Finnish)grpmax	0.00213%	46,919
African / African-American	0.00175%	57,238

Remaining individuals 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.Arg202Ser
Coding: c.606G>T
MANE Select: NM_014008
Type: single nucleotide variant
Location: chrX:49243354 (GRCh38)
Structure: AlphaFold pLDDT 78.95 · 4 PDB
Residue 202: 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-arg202ser (accessed [today's date]).

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