Is CC2D2A p.Asp19Val (c.56A>T) pathogenic?

CC2D2A p.Asp19Val (c.56A>T) is classified Uncertain significance in CC2D2A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-24). AlphaMissense: likely benign (0.0884); Very rare (popmax 0.00548%, nfe); Associated with Meckel syndrome.

What condition is associated with CC2D2A p.Asp19Val (c.56A>T)?

CC2D2A p.Asp19Val (c.56A>T) is associated with Meckel syndrome, Joubert syndrome (ClinVar).

How common is CC2D2A p.Asp19Val (c.56A>T) in the general population?

CC2D2A p.Asp19Val (c.56A>T) is very rare (popmax 0.00548%, nfe) (gnomAD).

What do computational predictors say about CC2D2A p.Asp19Val (c.56A>T)?

AlphaMissense predicts likely benign (score 0.0884) — an in-silico prediction, not a clinical call.

CC2D2A p.Asp19Val

c.56A>T · rs1403239059 · VCV969124

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0884 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00548%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Meckel syndrome

Computational evidence

Protein change
AlphaMissense	0.0884	likely benign
REVEL	0.043	moderately benign-leaning
SaProt	LLR -6.05	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 1.9	GERP -2.6, phastCons 0.001
Regional constraint	o/e 0.96	unconstrained · MANE · 104 kb · p 0.09 · regional, not allelic
Overall
CADD	18.6	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 0.00548% European (non-Finnish) · 63/1,148,606 alleles

Filtering AF 0.00438% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00398%

Overall 0.00418% 65/1,554,514 alleles · very rare exomes 62/1,402,300 · genomes 3/152,214 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00548%	18,232
Remaining individualsnot grpmax-eligible	0.00331%	30,195

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.Asp19Val
Coding: c.56A>T
MANE Select: NM_001378615
dbSNP: rs1403239059
Type: single nucleotide variant
Location: chr4:15478739 (GRCh38)
Gene constraint: LOEUF 0.854 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 69.46
Residue 19: the 'disordered' region

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.Asp19His 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
CC2D2A c.2004-17A>G Pathogenic/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-asp19val (accessed [today's date]).

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