Is CC2D2A p.Ser1106fs (c.3317_3318del) pathogenic?

CC2D2A p.Ser1106fs (c.33173318del) is classified Likely pathogenic in CC2D2A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-01). Very rare (popmax 0.00447%, eas); Associated with Meckel syndrome, type 6.

What condition is associated with CC2D2A p.Ser1106fs (c.3317_3318del)?

CC2D2A p.Ser1106fs (c.3317_3318del) is associated with Meckel syndrome, type 6, Joubert syndrome 9, retinitis pigmentosa 93 (ClinVar).

How common is CC2D2A p.Ser1106fs (c.3317_3318del) in the general population?

CC2D2A p.Ser1106fs (c.3317_3318del) is very rare (popmax 0.00447%, eas) (gnomAD).

CC2D2A p.Ser1106fs

c.3317_3318del · VCV3382135

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00447%, eas)

Conditions

Meckel syndrome, type 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 26 of 37
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.8, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00447% East Asian · 2/44,712 alleles

Filtering AF 0.000741% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000277%

Overall 0.000125% 2/1,605,168 alleles · very rare exomes 2/1,452,896 · genomes 0/152,272 · joint denominator

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: CC2D2A
Protein: p.Ser1106fs
Coding: c.3317_3318del
MANE Select: NM_001378615
Type: Microsatellite
Location: chr4:15567702 (GRCh38)
Gene constraint: LOEUF 0.854 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 69.46
Residue 1106: the c2 domain

Full CC2D2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Meckel syndrome, type 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Joubert syndrome 9 retinitis pigmentosa 93 COACH syndrome 2

Similar variants

CC2D2A c.3975+4_3975+7del Pathogenic ★★ same condition
CC2D2A p.Glu229del Benign/Likely benign ★★ same condition
CC2D2A p.Thr1341fs Pathogenic ★ same condition
CC2D2A c.248-4_248-3insAAGTTTT Conflicting classifications of pathogenicity ★ same condition
CC2D2A c.4315-6_4315-3del Conflicting classifications of pathogenicity ★ same condition
CC2D2A p.Glu1000del Conflicting classifications of pathogenicity ★ same condition
CC2D2A p.Ser1615fs Conflicting classifications of pathogenicity ★ same condition
CC2D2A c.1017+1G>A Pathogenic/Likely pathogenic ★★ same condition

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/cc2d2a-p-ser1106fs (accessed [today's date]).

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