Is CC2D2A p.Arg910Ter (c.2728C>T) pathogenic?

CC2D2A p.Arg910Ter (c.2728C>T) is classified Pathogenic in CC2D2A (ClinVar, Multiple submitters, 6 submitters; last evaluated 2024-11-27). Very rare (popmax 0.00446%, eas); Associated with Meckel syndrome.

What condition is associated with CC2D2A p.Arg910Ter (c.2728C>T)?

CC2D2A p.Arg910Ter (c.2728C>T) is associated with Meckel syndrome, Meckel syndrome, type 6, Joubert syndrome (ClinVar).

How common is CC2D2A p.Arg910Ter (c.2728C>T) in the general population?

CC2D2A p.Arg910Ter (c.2728C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

CC2D2A p.Arg910Ter

c.2728C>T · rs781206278 · VCV982064

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Conditions

Meckel syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 21 of 37
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1	GERP 1.1, phastCons 1
Overall
CADD	38.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,826 alleles

Filtering AF 0.00074% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000277%

Overall 0.000434% 7/1,613,236 alleles · very rare exomes 7/1,461,024 · genomes 0/152,212 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,413
South Asian	0.0022%	45,523
Remaining individualsnot grpmax-eligible	0.0016%	62,468
African / African-American	0.00133%	75,000
European (non-Finnish)	8.48e-05%	1,179,454

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.Arg910Ter
Coding: c.2728C>T
MANE Select: NM_001378615
dbSNP: rs781206278
Type: single nucleotide variant
Location: chr4:15557406 (GRCh38)
Gene constraint: LOEUF 0.854 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 69.46

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

Disease context

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

Also linked: Meckel syndrome, type 6 Joubert syndrome inherited retinal dystrophy

Similar variants

CC2D2A p.Arg910Gln Uncertain significance ★ ⚠ same residue
CC2D2A p.Arg910= Likely benign ★ same residue
CC2D2A c.1017+1G>A Pathogenic/Likely pathogenic ★★ same condition
CC2D2A c.123+2T>G Likely pathogenic ★★ same condition
CC2D2A c.1359+1G>A Pathogenic/Likely pathogenic ★★ same condition
CC2D2A c.1359+1G>C Likely pathogenic ★★ same condition
CC2D2A c.1466+1G>A Likely pathogenic ★★ same condition
CC2D2A c.1466+2T>C 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-arg910ter (accessed [today's date]).

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