Is CCDC12 p.Ala134Ser (c.400G>T) pathogenic?

CCDC12 p.Ala134Ser (c.400G>T) is classified Uncertain significance in CCDC12 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-26). AlphaMissense: likely benign (0.3038); Absent from gnomAD v4.1.

How common is CCDC12 p.Ala134Ser (c.400G>T) in the general population?

CCDC12 p.Ala134Ser (c.400G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCDC12 p.Ala134Ser (c.400G>T)?

AlphaMissense predicts likely benign (score 0.3038) — an in-silico prediction, not a clinical call.

CCDC12 p.Ala134Ser

c.400G>T · VCV3485923

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3038 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3038	likely benign
REVEL	0.722	pathogenic-leaning
SaProt	LLR -10.82	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 1.6, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 55 kb · p 0.41 · regional, not allelic
Overall
CADD	26.8	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.Ala134Ser
Coding: c.400G>T
MANE Select: NM_001277074
Type: single nucleotide variant
Location: chr3:46922254 (GRCh38)
Gene constraint: LOEUF 1.568 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.01 · 6 PDB
Residue 134: an α-helix

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.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
CCDC12 p.Arg26Trp 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-ala134ser (accessed [today's date]).

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