Is CC2D2A p.Ala96Thr (c.286G>A) pathogenic?

CC2D2A p.Ala96Thr (c.286G>A) is classified Conflicting classifications of pathogenicity in CC2D2A (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-09-15). AlphaMissense: likely benign (0.1454); Ultra-rare (popmax 0.0148%, afr); Associated with Inborn genetic diseases.

What condition is associated with CC2D2A p.Ala96Thr (c.286G>A)?

CC2D2A p.Ala96Thr (c.286G>A) is associated with Inborn genetic diseases, Joubert syndrome, Meckel syndrome (ClinVar).

How common is CC2D2A p.Ala96Thr (c.286G>A) in the general population?

CC2D2A p.Ala96Thr (c.286G>A) is ultra-rare (popmax 0.0148%, afr) (gnomAD).

What do computational predictors say about CC2D2A p.Ala96Thr (c.286G>A)?

AlphaMissense predicts likely benign (score 0.1454) — an in-silico prediction, not a clinical call.

CC2D2A p.Ala96Thr

c.286G>A · rs376438052 · VCV420568

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1454 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0148%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1454	likely benign
REVEL	0.056	moderately benign-leaning
SaProt	LLR -6.03	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 9.6	GERP 2.6, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 104 kb · p 0.09 · regional, not allelic
Overall
CADD	24.2	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

Grpmax group 0.0148% African / African-American · 11/74,158 alleles

Filtering AF 0.00823% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00639%

Overall 0.000809% 13/1,607,680 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0148%	6,742
Admixed American	0.00169%	59,188
Remaining individualsnot grpmax-eligible	0.00161%	62,304

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.Ala96Thr
Coding: c.286G>A
MANE Select: NM_001378615
dbSNP: rs376438052
Type: single nucleotide variant
Location: chr4:15502467 (GRCh38)
Gene constraint: LOEUF 0.854 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 69.46
Residue 96: the 'disordered' region

Full CC2D2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Joubert syndrome Meckel syndrome

Similar variants

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
CC2D2A c.2486+1G>A 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-ala96thr (accessed [today's date]).

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