Is CC2D2A p.Asn482Asp (c.1444A>G) pathogenic?

CC2D2A p.Asn482Asp (c.1444A>G) is classified Uncertain significance in CC2D2A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-07). AlphaMissense: likely benign (0.1054); Very rare (popmax 0.00669%, amr); Associated with COACH syndrome 2.

What condition is associated with CC2D2A p.Asn482Asp (c.1444A>G)?

CC2D2A p.Asn482Asp (c.1444A>G) is associated with COACH syndrome 2, Meckel syndrome, type 6, Joubert syndrome 9 (ClinVar).

How common is CC2D2A p.Asn482Asp (c.1444A>G) in the general population?

CC2D2A p.Asn482Asp (c.1444A>G) is very rare (popmax 0.00669%, amr) (gnomAD).

How is Joubert syndrome with hepatic defect inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CC2D2A p.Asn482Asp (c.1444A>G)?

AlphaMissense predicts likely benign (score 0.1054) — an in-silico prediction, not a clinical call.

CC2D2A p.Asn482Asp

c.1444A>G · rs777022662 · VCV1419788

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1054 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00669%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

COACH syndrome 2

Computational evidence

Protein change
AlphaMissense	0.1054	likely benign
REVEL	0.248	benign-leaning
SaProt	LLR -5.96	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 5.2	GERP 1.2, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 104 kb · p 0.09 · regional, not allelic
Overall
CADD	17.09	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

Grpmax group 0.00669% Admixed American · 4/59,790 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000248% 4/1,612,160 alleles · very rare exomes 4/1,459,804 · genomes 0/152,356 · 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.Asn482Asp
Coding: c.1444A>G
MANE Select: NM_001378615
dbSNP: rs777022662
Type: single nucleotide variant
Location: chr4:15528704 (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

COACH syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Meckel syndrome, type 6 Joubert syndrome 9 Joubert syndrome Meckel syndrome retinitis pigmentosa 93

For Joubert syndrome with hepatic defect (Orphanet):

Inheritance: Autosomal recessive
Onset: Neonatal

Similar variants

CC2D2A c.1017+1G>A Pathogenic/Likely pathogenic ★★ same condition
CC2D2A c.1149+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
CC2D2A c.1608-2A>G 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-asn482asp (accessed [today's date]).

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