Is CC2D2A p.Pro1054Ser (c.3160C>T) pathogenic?

CC2D2A p.Pro1054Ser (c.3160C>T) is classified Uncertain significance in CC2D2A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-02). AlphaMissense: likely pathogenic (0.8898); Absent from gnomAD v4.1; Associated with Meckel syndrome.

What condition is associated with CC2D2A p.Pro1054Ser (c.3160C>T)?

CC2D2A p.Pro1054Ser (c.3160C>T) is associated with Meckel syndrome, Joubert syndrome (ClinVar).

How common is CC2D2A p.Pro1054Ser (c.3160C>T) in the general population?

CC2D2A p.Pro1054Ser (c.3160C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CC2D2A p.Pro1054Ser (c.3160C>T)?

AlphaMissense predicts likely pathogenic (score 0.8898) — an in-silico prediction, not a clinical call.

CC2D2A p.Pro1054Ser

c.3160C>T · rs1719718448 · VCV938538

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8898 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Meckel syndrome

Computational evidence

Protein change
AlphaMissense	0.8898	likely pathogenic · top 8% in CC2D2A
REVEL	0.665	pathogenic-leaning
SaProt	LLR -10.89	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.7, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 104 kb · p 0.09 · regional, not allelic
Overall
CADD	24.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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.Pro1054Ser
Coding: c.3160C>T
MANE Select: NM_001378615
dbSNP: rs1719718448
Type: single nucleotide variant
Location: chr4:15563500 (GRCh38)
Gene constraint: LOEUF 0.854 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 69.46
Residue 1054: the c2 domain

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

Similar variants

CC2D2A p.Pro1054Thr Uncertain significance ★★ ⚠ same residue
CC2D2A p.Pro1054Leu Uncertain significance ★ ⚠ 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>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-pro1054ser (accessed [today's date]).

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