Is CC2D1B p.Arg502Gln (c.1505G>A) pathogenic?

CC2D1B p.Arg502Gln (c.1505G>A) is classified Likely benign in CC2D1B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-24). AlphaMissense: likely benign (0.0583); Ultra-rare (popmax 0.0341%, mid).

How common is CC2D1B p.Arg502Gln (c.1505G>A) in the general population?

CC2D1B p.Arg502Gln (c.1505G>A) is ultra-rare (popmax 0.0341%, mid) (gnomAD).

What do computational predictors say about CC2D1B p.Arg502Gln (c.1505G>A)?

AlphaMissense predicts likely benign (score 0.0583) — an in-silico prediction, not a clinical call.

CC2D1B p.Arg502Gln

c.1505G>A · VCV3996232

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0583 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0341%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0583	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -5.78	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 3.4	GERP -1.1, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 11 kb · p 0.15 · regional, not allelic
Overall
CADD	12.38	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 R508Q vs ClinVar R502Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0341% Middle Eastern · 2/5,868 alleles

Filtering AF 0.0144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.012%

Overall 0.00246% 39/1,586,610 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0341%	2,934
South Asian	0.0221%	4,530
Remaining individualsnot grpmax-eligible	0.00327%	30,622
European (non-Finnish)	0.00137%	73,036

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.Arg502Gln
Coding: c.1505G>A
MANE Select: NM_001330585
Type: single nucleotide variant
Location: chr1:52357855 (GRCh38)
Gene constraint: LOEUF 0.978 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.98
Residue 502: the 'disordered' region

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

Similar variants

CC2D1B p.Arg502Trp 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-arg502gln (accessed [today's date]).

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