Is CCDC22 p.Ser319Tyr (c.956C>A) pathogenic?

CCDC22 p.Ser319Tyr (c.956C>A) is classified Uncertain significance in CCDC22 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-12-16). AlphaMissense: likely benign (0.1453); Absent from gnomAD v4.1; Associated with CCDC22-related disorder.

What condition is associated with CCDC22 p.Ser319Tyr (c.956C>A)?

CCDC22 p.Ser319Tyr (c.956C>A) is associated with CCDC22-related disorder (ClinVar).

How common is CCDC22 p.Ser319Tyr (c.956C>A) in the general population?

CCDC22 p.Ser319Tyr (c.956C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCDC22 p.Ser319Tyr (c.956C>A)?

AlphaMissense predicts likely benign (score 0.1453) — an in-silico prediction, not a clinical call.

CCDC22 p.Ser319Tyr

c.956C>A · rs781882275 · VCV3055673

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1453 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,199,190)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CCDC22-related disorder

Computational evidence

Protein change
AlphaMissense	0.1453	likely benign
REVEL	0.079	moderately benign-leaning
SaProt	LLR -9.03	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 4.4	GERP 1.6, phastCons 0.99
Regional constraint	o/e 0.99	unconstrained · MANE · 5,832 bp · p 0.85 · regional, not allelic
Overall
CADD	21.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,199,190). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CCDC22
Protein: p.Ser319Tyr
Coding: c.956C>A
MANE Select: NM_014008
dbSNP: rs781882275
Type: single nucleotide variant
Location: chrX:49247542 (GRCh38)
Structure: AlphaFold pLDDT 78.95 · 4 PDB
Residue 319: 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

Disease context

CCDC22-related disorder

Similar variants

CCDC22 p.Gln569Glu Uncertain significance ★★ ⚠ same condition
CCDC22 p.Pro141Thr Uncertain significance ★ ⚠ same condition
CCDC22 p.Arg607Gln Uncertain significance ⚠ same condition
CCDC22 p.Gln364Pro Uncertain significance ⚠ same condition
CCDC22 c.51-9C>T Likely benign same condition
CCDC22 p.Arg607Trp 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-ser319tyr (accessed [today's date]).

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