Is CC2D2A p.Phe1195fs (c.3584del) pathogenic?

CC2D2A p.Phe1195fs (c.3584del) is classified Likely pathogenic in CC2D2A (ClinVar, No assertion criteria, 1 submitter). Ultra-rare (popmax 0.0166%, mid); Associated with Meckel syndrome, type 6.

What condition is associated with CC2D2A p.Phe1195fs (c.3584del)?

CC2D2A p.Phe1195fs (c.3584del) is associated with Meckel syndrome, type 6 (ClinVar).

How common is CC2D2A p.Phe1195fs (c.3584del) in the general population?

CC2D2A p.Phe1195fs (c.3584del) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

CC2D2A p.Phe1195fs

c.3584del · rs386833756 · VCV56308

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

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 28 of 37
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0166% Middle Eastern · 1/6,030 alleles

Overall 6.25e-05% 1/1,600,060 alleles · ultra-rare exomes 1/1,447,766 · genomes 0/152,294 · 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.Phe1195fs
Coding: c.3584del
MANE Select: NM_001378615
dbSNP: rs386833756
Type: Deletion
Location: chr4:15570484 (GRCh38)
Gene constraint: LOEUF 0.854 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 69.46
Residue 1195: 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

Similar variants

CC2D2A c.3289delG Pathogenic ★★ same condition
CC2D2A c.3597_3600del Pathogenic/Likely pathogenic ★★ same condition
CC2D2A c.4179+1del Pathogenic ★★ same condition
CC2D2A p.Ala1197fs Pathogenic/Likely pathogenic ★★ same condition
CC2D2A p.Ala447fs Pathogenic/Likely pathogenic ★★ same condition
CC2D2A p.Asp1227fs Likely pathogenic ★★ same condition
CC2D2A p.Asp1489fs Pathogenic/Likely pathogenic ★★ same condition
CC2D2A p.Gln280fs 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-phe1195fs (accessed [today's date]).

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