Is CC2D2A p.Glu243Asp (c.729A>T) pathogenic?

CC2D2A p.Glu243Asp (c.729A>T) is classified Uncertain significance in CC2D2A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-13). AlphaMissense: likely benign (0.0867); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CC2D2A p.Glu243Asp (c.729A>T)?

CC2D2A p.Glu243Asp (c.729A>T) is associated with Inborn genetic diseases (ClinVar).

How common is CC2D2A p.Glu243Asp (c.729A>T) in the general population?

CC2D2A p.Glu243Asp (c.729A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CC2D2A p.Glu243Asp (c.729A>T)?

AlphaMissense predicts likely benign (score 0.0867) — an in-silico prediction, not a clinical call.

CC2D2A p.Glu243Asp

c.729A>T · VCV4606675

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0867 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0867	likely benign
REVEL	0.012	strongly benign-leaning
SaProt	LLR -6.54	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 0.41	GERP -2.2, phastCons 0.027
Regional constraint	o/e 0.96	unconstrained · MANE · 104 kb · p 0.09 · regional, not allelic
Overall
CADD	4.838	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

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.Glu243Asp
Coding: c.729A>T
MANE Select: NM_001378615
Type: single nucleotide variant
Location: chr4:15514718 (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

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

Similar variants

CC2D2A p.Glu243= Likely benign ★ same residue
CC2D2A p.Val1045Ala Pathogenic/Likely pathogenic ★★ same condition
CC2D2A p.Ala323Thr Uncertain significance ★★ ⚠ same condition
CC2D2A p.Ala669Glu Uncertain significance ★★ ⚠ same condition
CC2D2A p.Arg1028Gln Uncertain significance ★★ same condition
CC2D2A p.Arg1028Trp Uncertain significance ★★ same condition
CC2D2A p.Arg1168His Uncertain significance ★★ ⚠ same condition
CC2D2A p.Arg1177His Uncertain significance ★★ ⚠ 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-glu243asp (accessed [today's date]).

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