Is CCDC112 p.Ala165Val (c.494C>T) pathogenic?

CCDC112 p.Ala165Val (c.494C>T) is classified Uncertain significance in CCDC112 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-24). AlphaMissense: likely benign (0.3294); Absent from gnomAD v4.1.

How common is CCDC112 p.Ala165Val (c.494C>T) in the general population?

CCDC112 p.Ala165Val (c.494C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCDC112 p.Ala165Val (c.494C>T)?

AlphaMissense predicts likely benign (score 0.3294) — an in-silico prediction, not a clinical call.

CCDC112 p.Ala165Val

c.494C>T · VCV3996323

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3294 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3294	likely benign
REVEL	0.162	moderately benign-leaning
SaProt	LLR -7.43	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.31	donor gain · deltas
Pangolin	Δ0.23	gain · loss 0.18 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 29 kb · p 0.025 · regional, not allelic
Overall
CADD	33.0	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A82V vs ClinVar A165V) — 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.Ala165Val
Coding: c.494C>T
MANE Select: NM_001040440
Type: single nucleotide variant
Location: chr5:115276027 (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.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
CCDC112 p.Arg51Cys 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-ala165val (accessed [today's date]).

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