Is CCDC12 p.Glu96Lys (c.286G>A) pathogenic?

CCDC12 p.Glu96Lys (c.286G>A) is classified Uncertain significance in CCDC12 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-10). AlphaMissense: likely benign (0.1318); Ultra-rare (popmax 0.0205%, eas).

How common is CCDC12 p.Glu96Lys (c.286G>A) in the general population?

CCDC12 p.Glu96Lys (c.286G>A) is ultra-rare (popmax 0.0205%, eas) (gnomAD).

What do computational predictors say about CCDC12 p.Glu96Lys (c.286G>A)?

AlphaMissense predicts likely benign (score 0.1318) — an in-silico prediction, not a clinical call.

CCDC12 p.Glu96Lys

c.286G>A · rs566710688 · VCV3138286

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1318 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0205%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1318	likely benign
REVEL	0.163	moderately benign-leaning
SaProt	LLR -9.77	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 4.7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 55 kb · p 0.41 · regional, not allelic
Overall
CADD	22.2	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 0.0205% East Asian · 9/43,992 alleles

Filtering AF 0.0106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00793%

Overall 0.00151% 24/1,589,294 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0205%	4,888
Remaining individualsnot grpmax-eligible	0.00326%	30,721
South Asian	0.00115%	87,308
European (non-Finnish)	0.00103%	97,233

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: CCDC12
Protein: p.Glu96Lys
Coding: c.286G>A
MANE Select: NM_001277074
dbSNP: rs566710688
Type: single nucleotide variant
Location: chr3:46923627 (GRCh38)
Gene constraint: LOEUF 1.568 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.01 · 6 PDB

Full CCDC12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NBEAL2 c.51+18C>T Benign/Likely benign ★★ same type
CCDC12 c.-3A>G Uncertain significance ★ same type
CCDC12 p.Ala134Ser Uncertain significance ★ ⚠ same type
CCDC12 p.Ala151Pro Uncertain significance ★ ⚠ same type
CCDC12 p.Ala3Val Uncertain significance ★ ⚠ same type
CCDC12 p.Ala93Ser Uncertain significance ★ ⚠ same type
CCDC12 p.Arg130Gln Uncertain significance ★ ⚠ same type
CCDC12 p.Arg26Pro 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/ccdc12-p-glu96lys (accessed [today's date]).

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