Is CC2D2A p.Arg699Gln (c.2096G>A) pathogenic?

CC2D2A p.Arg699Gln (c.2096G>A) is classified Uncertain significance in CC2D2A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-04). AlphaMissense: likely benign (0.0902); Very rare (popmax 0.00559%, amr); Associated with Inborn genetic diseases.

What condition is associated with CC2D2A p.Arg699Gln (c.2096G>A)?

CC2D2A p.Arg699Gln (c.2096G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CC2D2A p.Arg699Gln (c.2096G>A) in the general population?

CC2D2A p.Arg699Gln (c.2096G>A) is very rare (popmax 0.00559%, amr) (gnomAD).

What do computational predictors say about CC2D2A p.Arg699Gln (c.2096G>A)?

AlphaMissense predicts likely benign (score 0.0902) — an in-silico prediction, not a clinical call.

CC2D2A p.Arg699Gln

c.2096G>A · VCV3996251

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0902 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00559%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0902	likely benign
REVEL	0.151	moderately benign-leaning
SaProt	LLR -4.00	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6.5	GERP 2.3, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 104 kb · p 0.09 · regional, not allelic
Overall
CADD	28.4	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 0.00559% Admixed American · 3/53,628 alleles

Filtering AF 0.00148% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000811%

Overall 0.000636% 10/1,572,948 alleles · very rare exomes 9/1,420,834 · genomes 1/152,114 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00559%	17,876
South Asian	0.00234%	42,672
European (non-Finnish)	0.000431%	231,784

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.Arg699Gln
Coding: c.2096G>A
MANE Select: NM_001378615
Type: single nucleotide variant
Location: chr4:15540929 (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.Arg699Leu Uncertain significance ★ ⚠ same residue
CC2D2A p.Arg699Trp Uncertain significance ★ ⚠ 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

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-arg699gln (accessed [today's date]).

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