Is CC2D2B p.Ile1260Ser (c.3779T>G) pathogenic?

CC2D2B p.Ile1260Ser (c.3779T>G) is classified Uncertain significance in CC2D2B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-28). AlphaMissense: likely benign (0.2447); Rare (popmax 0.116%, sas).

How common is CC2D2B p.Ile1260Ser (c.3779T>G) in the general population?

CC2D2B p.Ile1260Ser (c.3779T>G) is rare (popmax 0.116%, sas) (gnomAD).

What do computational predictors say about CC2D2B p.Ile1260Ser (c.3779T>G)?

AlphaMissense predicts likely benign (score 0.2447) — an in-silico prediction, not a clinical call.

CC2D2B p.Ile1260Ser

c.3779T>G · rs764293033 · VCV2601402

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2447 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.116%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2447	likely benign
REVEL	0.623	indeterminate
SaProt	LLR -9.88	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 0.38, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 41 kb · p 0.0003 · regional, not allelic
Overall
CADD	25.5	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 0.116% South Asian · 101/86,894 alleles

Filtering AF 0.0979% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.091%

Overall 0.00678% 108/1,592,708 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.116%	860
Remaining individualsnot grpmax-eligible	0.00974%	10,263
European (non-Finnish)	8.53e-05%	1,172,853

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.Ile1260Ser
Coding: c.3779T>G
MANE Select: NM_001349008
dbSNP: rs764293033
Type: single nucleotide variant
Location: chr10:96019715 (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-ile1260ser (accessed [today's date]).

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