Is CC2D2B p.Pro1266Thr (c.3796C>A) pathogenic?

CC2D2B p.Pro1266Thr (c.3796C>A) is classified Uncertain significance in CC2D2B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-22). AlphaMissense: likely benign (0.3139); Ultra-rare (popmax 0.0135%, afr).

How common is CC2D2B p.Pro1266Thr (c.3796C>A) in the general population?

CC2D2B p.Pro1266Thr (c.3796C>A) is ultra-rare (popmax 0.0135%, afr) (gnomAD).

What do computational predictors say about CC2D2B p.Pro1266Thr (c.3796C>A)?

AlphaMissense predicts likely benign (score 0.3139) — an in-silico prediction, not a clinical call.

CC2D2B p.Pro1266Thr

c.3796C>A · VCV3263734

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3139 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0135%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3139	likely benign
REVEL	0.57	indeterminate
SaProt	LLR -11.31	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 41 kb · p 0.0003 · regional, not allelic
Overall
CADD	24.1	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 0.0135% African / African-American · 10/73,866 alleles

Filtering AF 0.00732% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00557%

Overall 0.000875% 14/1,599,698 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0135%	7,387
Remaining individualsnot grpmax-eligible	0.00323%	30,968
South Asian	0.00113%	88,242
European (non-Finnish)	8.52e-05%	1,174,109

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: CC2D2B
Protein: p.Pro1266Thr
Coding: c.3796C>A
MANE Select: NM_001349008
Type: single nucleotide variant
Location: chr10:96019732 (GRCh38)
Gene constraint: LOEUF 0.832 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.49

Full CC2D2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CC2D2B p.Arg1101Gln Uncertain significance ★ ⚠ same type
CC2D2B p.Arg1329Gln Uncertain significance ★ ⚠ same type
CC2D2B p.Arg1345Pro Uncertain significance ★ ⚠ same type
CC2D2B p.Asn1422Ser Uncertain significance ★ ⚠ same type
CC2D2B p.Asp1248Asn Uncertain significance ★ ⚠ same type
CC2D2B p.Asp1312Glu Uncertain significance ★ ⚠ same type
CC2D2B p.Cys1234Arg Uncertain significance ★ ⚠ same type
CC2D2B p.Cys985Tyr 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/cc2d2b-p-pro1266thr (accessed [today's date]).

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