Is CC2D2A p.Val1430Ala (c.4289T>C) pathogenic?

CC2D2A p.Val1430Ala (c.4289T>C) is classified Pathogenic/Likely pathogenic in CC2D2A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-06-20). AlphaMissense: likely benign (0.1918); Absent from gnomAD v4.1; Associated with Meckel syndrome.

What condition is associated with CC2D2A p.Val1430Ala (c.4289T>C)?

CC2D2A p.Val1430Ala (c.4289T>C) is associated with Meckel syndrome, Joubert syndrome 9, Joubert syndrome (ClinVar).

How common is CC2D2A p.Val1430Ala (c.4289T>C) in the general population?

CC2D2A p.Val1430Ala (c.4289T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CC2D2A p.Val1430Ala (c.4289T>C)?

AlphaMissense predicts likely benign (score 0.1918) — an in-silico prediction, not a clinical call.

CC2D2A p.Val1430Ala

c.4289T>C · rs863225168 · VCV217594

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1918 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Meckel syndrome

Computational evidence

Protein change
AlphaMissense	0.1918	likely benign ⚠ discordant with ClinVar
REVEL	0.766	pathogenic-leaning
SaProt	LLR -10.02	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 2.3, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 14 kb · p 0.69 · regional, not allelic
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CC2D2A
Protein: p.Val1430Ala
Coding: c.4289T>C
MANE Select: NM_001378615
dbSNP: rs863225168
Type: single nucleotide variant
Location: chr4:15589654 (GRCh38)
Gene constraint: LOEUF 0.854 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 69.46
Residue 1430: a UniProt-annotated variant site (in jbts9)

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: Joubert syndrome 9 Joubert syndrome

Similar variants

CC2D2A p.Val1430= Likely benign ★ 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-val1430ala (accessed [today's date]).

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