Is CC2D2A p.Tyr387= (c.1161C>T) pathogenic?

CC2D2A p.Tyr387= (c.1161C>T) is classified Conflicting classifications of pathogenicity in CC2D2A (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-12-09). Very rare (popmax 0.00267%, afr); Associated with COACH syndrome 2.

What condition is associated with CC2D2A p.Tyr387= (c.1161C>T)?

CC2D2A p.Tyr387= (c.1161C>T) is associated with COACH syndrome 2, Meckel syndrome, type 6, Joubert syndrome 9 (ClinVar).

How common is CC2D2A p.Tyr387= (c.1161C>T) in the general population?

CC2D2A p.Tyr387= (c.1161C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

How is Joubert syndrome with hepatic defect inherited?

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

CC2D2A p.Tyr387=

c.1161C>T · rs1717568150 · VCV2068455

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

COACH syndrome 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP -4.6	GERP -5.5
Overall
CADD	0.359	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/75,024 alleles

Filtering AF 0.000442% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.00048% 7/1,459,664 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,512
East Asian	0.00223%	44,858
European (non-Finnish)	0.000339%	294,662

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.Tyr387=
Coding: c.1161C>T
MANE Select: NM_001378615
dbSNP: rs1717568150
Type: single nucleotide variant
Location: chr4:15527458 (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 p.Tyr387Ter Pathogenic ★ same residue
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

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-tyr387 (accessed [today's date]).

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