Is CCDC12 p.Val8Met (c.22G>A) pathogenic?

CCDC12 p.Val8Met (c.22G>A) is classified Uncertain significance in CCDC12 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-11). AlphaMissense: ambiguous (0.5106); Absent from gnomAD v4.1.

How common is CCDC12 p.Val8Met (c.22G>A) in the general population?

CCDC12 p.Val8Met (c.22G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCDC12 p.Val8Met (c.22G>A)?

AlphaMissense predicts ambiguous (score 0.5106) — an in-silico prediction, not a clinical call.

CCDC12 p.Val8Met

c.22G>A · VCV3485925

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5106 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5106	ambiguous
REVEL	0.07	moderately benign-leaning
SaProt	LLR -7.72	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.16	GERP 1.5, phastCons 0.094
Regional constraint	o/e 0.94	unconstrained · MANE · 55 kb · p 0.41 · regional, not allelic
Overall
CADD	21.6	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: CCDC12
Protein: p.Val8Met
Coding: c.22G>A
MANE Select: NM_001277074
Type: single nucleotide variant
Location: chr3:46976711 (GRCh38)
Gene constraint: LOEUF 1.568 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.01 · 6 PDB
Residue 8: the 'disordered' region

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-val8met (accessed [today's date]).

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