Is CC2D1B p.Arg798Trp (c.2392C>T) pathogenic?

CC2D1B p.Arg798Trp (c.2392C>T) is classified Uncertain significance in CC2D1B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-15). AlphaMissense: likely benign (0.1371); Very rare (popmax 0.00446%, eas).

How common is CC2D1B p.Arg798Trp (c.2392C>T) in the general population?

CC2D1B p.Arg798Trp (c.2392C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about CC2D1B p.Arg798Trp (c.2392C>T)?

AlphaMissense predicts likely benign (score 0.1371) — an in-silico prediction, not a clinical call.

CC2D1B p.Arg798Trp

c.2392C>T · VCV4648839

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1371 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1371	likely benign
REVEL	0.24	benign-leaning
SaProt	LLR -11.68	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.1	GERP 1.3, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 11 kb · p 0.15 · regional, not allelic
Overall
CADD	28.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R804W vs ClinVar R798W) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,892 alleles

Filtering AF 0.00315% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00279%

Overall 0.00353% 57/1,614,002 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,446
European (non-Finnish)	0.00407%	24,584
South Asian	0.00329%	30,362
African / African-American	0.00267%	37,450
Admixed American	0.00167%	59,984
Remaining individualsnot grpmax-eligible	0.0016%	62,486

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: CC2D1B
Protein: p.Arg798Trp
Coding: c.2392C>T
MANE Select: NM_001330585
Type: single nucleotide variant
Location: chr1:52354646 (GRCh38)
Gene constraint: LOEUF 0.978 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.98
Residue 798: the c2 domain

Full CC2D1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CC2D1B p.Arg798Gln Uncertain significance ★ ⚠ same residue
CC2D1B p.Gly790= Benign ★★ same type
CC2D1B p.His674Tyr Likely benign ★★ same type
CC2D1B p.Leu511= Benign ★★ same type
CC2D1B p.Ala103Gly Uncertain significance ★ ⚠ same type
CC2D1B p.Ala180Ser Uncertain significance ★ ⚠ same type
CC2D1B p.Ala181Thr Uncertain significance ★ ⚠ same type
CC2D1B p.Ala181Val Uncertain significance ★ ⚠ same type

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/cc2d1b-p-arg798trp (accessed [today's date]).

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