Is CC2D2B p.Ser1014Pro (c.3040T>C) pathogenic?

CC2D2B p.Ser1014Pro (c.3040T>C) is classified Uncertain significance in CC2D2B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-12). AlphaMissense: likely benign (0.1009); Absent from gnomAD v4.1.

How common is CC2D2B p.Ser1014Pro (c.3040T>C) in the general population?

CC2D2B p.Ser1014Pro (c.3040T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CC2D2B p.Ser1014Pro (c.3040T>C)?

AlphaMissense predicts likely benign (score 0.1009) — an in-silico prediction, not a clinical call.

CC2D2B p.Ser1014Pro

c.3040T>C · rs2496544177 · VCV2300578

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1009 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1009	likely benign
REVEL	0.253	benign-leaning
SaProt	LLR -10.82	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 41 kb · p 0.0003 · regional, not allelic
Overall
CADD	20.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CC2D2B
Protein: p.Ser1014Pro
Coding: c.3040T>C
MANE Select: NM_001349008
dbSNP: rs2496544177
Type: single nucleotide variant
Location: chr10:96009918 (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-ser1014pro (accessed [today's date]).

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