Is CCDC22 p.Arg607Trp (c.1819C>T) pathogenic?

CCDC22 p.Arg607Trp (c.1819C>T) is classified Likely benign in CCDC22 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-07-30). AlphaMissense: likely benign (0.1231); Rare (popmax 0.138%, afr); Associated with CCDC22-related disorder.

What condition is associated with CCDC22 p.Arg607Trp (c.1819C>T)?

CCDC22 p.Arg607Trp (c.1819C>T) is associated with CCDC22-related disorder (ClinVar).

How common is CCDC22 p.Arg607Trp (c.1819C>T) in the general population?

CCDC22 p.Arg607Trp (c.1819C>T) is rare (popmax 0.138%, afr) (gnomAD).

What do computational predictors say about CCDC22 p.Arg607Trp (c.1819C>T)?

AlphaMissense predicts likely benign (score 0.1231) — an in-silico prediction, not a clinical call.

CCDC22 p.Arg607Trp

c.1819C>T · rs139328507 · VCV3046839

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1231 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.138%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CCDC22-related disorder

Computational evidence

Protein change
AlphaMissense	0.1231	likely benign
REVEL	0.081	moderately benign-leaning
SaProt	LLR -12.33	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 0.44, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 582 bp · p 0.38 · regional, not allelic
Overall
CADD	21.9	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 0.138% African / African-American · 77/55,878 alleles

Filtering AF 0.113% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.104%

Overall 0.0115% 134/1,166,005 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.138%	726
Remaining individualsnot grpmax-eligible	0.0131%	7,653
South Asian	0.0057%	17,545
European (non-Finnish)	0.00528%	18,950
East Asian	0.00325%	30,804
Admixed American	0.00257%	38,949

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.Arg607Trp
Coding: c.1819C>T
MANE Select: NM_014008
dbSNP: rs139328507
Type: single nucleotide variant
Location: chrX:49250196 (GRCh38)
Structure: AlphaFold pLDDT 78.95 · 4 PDB

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

Disease context

CCDC22-related disorder

Similar variants

CCDC22 p.Arg607Gln Uncertain significance ⚠ same residue
CCDC22 p.Gln569Glu Uncertain significance ★★ ⚠ same condition
CCDC22 p.Pro141Thr Uncertain significance ★ ⚠ same condition
CCDC22 p.Gln364Pro Uncertain significance ⚠ same condition
CCDC22 p.Ser319Tyr Uncertain significance ⚠ same condition
CCDC22 c.51-9C>T Likely benign same condition
CCDC22 p.Leu429= Likely benign same condition
CCDC22 p.Ala463Gly 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-arg607trp (accessed [today's date]).

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