Is CCDC22 p.Val196Met (c.586G>A) pathogenic?

CCDC22 p.Val196Met (c.586G>A) is classified Conflicting classifications of pathogenicity in CCDC22 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-12-16). AlphaMissense: likely benign (0.2006); Very rare (popmax 0.00864%, nfe).

How common is CCDC22 p.Val196Met (c.586G>A) in the general population?

CCDC22 p.Val196Met (c.586G>A) is very rare (popmax 0.00864%, nfe) (gnomAD).

What do computational predictors say about CCDC22 p.Val196Met (c.586G>A)?

AlphaMissense predicts likely benign (score 0.2006) — an in-silico prediction, not a clinical call.

CCDC22 p.Val196Met

c.586G>A · rs782660215 · VCV1194570

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2006 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00864%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2006	likely benign
REVEL	0.082	moderately benign-leaning
SaProt	LLR -7.63	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 7.3	GERP 1.4, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 5,832 bp · p 0.85 · regional, not allelic
Overall
CADD	21.6	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 0.00864% European (non-Finnish) · 77/891,565 alleles

Filtering AF 0.00701% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00648%

Overall 0.00648% 78/1,203,297 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00864%	11,579
Remaining individualsnot grpmax-eligible	0.00211%	47,299

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.Val196Met
Coding: c.586G>A
MANE Select: NM_014008
dbSNP: rs782660215
Type: single nucleotide variant
Location: chrX:49243334 (GRCh38)
Structure: AlphaFold pLDDT 78.95 · 4 PDB
Residue 196: the 'sufficicient and required for interaction with ccdc93' region; a β-strand; 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-val196met (accessed [today's date]).

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