Is CCDC63 p.Thr65Ala (c.193A>G) pathogenic?

CCDC63 p.Thr65Ala (c.193A>G) is classified Uncertain significance in CCDC63 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-19). AlphaMissense: likely benign (0.0699); Absent from gnomAD v4.1.

How common is CCDC63 p.Thr65Ala (c.193A>G) in the general population?

CCDC63 p.Thr65Ala (c.193A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCDC63 p.Thr65Ala (c.193A>G)?

AlphaMissense predicts likely benign (score 0.0699) — an in-silico prediction, not a clinical call.

CCDC63 p.Thr65Ala

c.193A>G · VCV3997112

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0699 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0699	likely benign
REVEL	0.015	strongly benign-leaning
SaProt	LLR -5.50	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 0.26	GERP 0.012
Regional constraint	o/e 0.92	unconstrained · MANE · 55 kb · p 0.045 · regional, not allelic
Overall
CADD	11.05	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

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: CCDC63
Protein: p.Thr65Ala
Coding: c.193A>G
MANE Select: NM_152591
Type: single nucleotide variant
Location: chr12:110858599 (GRCh38)
Gene constraint: LOEUF 1.051 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.75

Full CCDC63 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC63 p.Ala108Thr Uncertain significance ★ ⚠ same type
CCDC63 p.Ala144Val Uncertain significance ★ ⚠ same type
CCDC63 p.Ala27Val Uncertain significance ★ ⚠ same type
CCDC63 p.Ala280Val Uncertain significance ★ ⚠ same type
CCDC63 p.Arg148Trp Uncertain significance ★ ⚠ same type
CCDC63 p.Arg230Gln Uncertain significance ★ ⚠ same type
CCDC63 p.Arg237Cys Uncertain significance ★ ⚠ same type
CCDC63 p.Arg237His 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/ccdc63-p-thr65ala (accessed [today's date]).

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