Is CCDC112 p.Val233Glu (c.698T>A) pathogenic?

CCDC112 p.Val233Glu (c.698T>A) is classified Uncertain significance in CCDC112 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-25). AlphaMissense: likely pathogenic (0.7946); Absent from gnomAD v4.1.

How common is CCDC112 p.Val233Glu (c.698T>A) in the general population?

CCDC112 p.Val233Glu (c.698T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCDC112 p.Val233Glu (c.698T>A)?

AlphaMissense predicts likely pathogenic (score 0.7946) — an in-silico prediction, not a clinical call.

CCDC112 p.Val233Glu

c.698T>A · rs2479345708 · VCV3138268

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7946 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7946	likely pathogenic · top 6% in CCDC112
REVEL	0.385	indeterminate
SaProt	LLR -12.03	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 29 kb · p 0.025 · regional, not allelic
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM V150E vs ClinVar V233E) — verify the residue.

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: CCDC112
Protein: p.Val233Glu
Coding: c.698T>A
MANE Select: NM_001040440
dbSNP: rs2479345708
Type: single nucleotide variant
Location: chr5:115275436 (GRCh38)
Gene constraint: LOEUF 0.875 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.18

Full CCDC112 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC112 p.Ala165Val Uncertain significance ★ ⚠ same type
CCDC112 p.Ala299Ser Uncertain significance ★ ⚠ same type
CCDC112 p.Ala434Pro Uncertain significance ★ ⚠ same type
CCDC112 p.Ala68Pro Uncertain significance ★ same type
CCDC112 p.Arg391Cys Uncertain significance ★ ⚠ same type
CCDC112 p.Arg391His Uncertain significance ★ ⚠ same type
CCDC112 p.Arg391Leu Uncertain significance ★ ⚠ same type
CCDC112 p.Arg393Leu 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/ccdc112-p-val233glu (accessed [today's date]).

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