Is CCDC63 p.Ser377Pro (c.1129T>C) pathogenic?

CCDC63 p.Ser377Pro (c.1129T>C) is classified Uncertain significance in CCDC63 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-03). AlphaMissense: likely benign (0.3167); Absent from gnomAD v4.1.

How common is CCDC63 p.Ser377Pro (c.1129T>C) in the general population?

CCDC63 p.Ser377Pro (c.1129T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCDC63 p.Ser377Pro (c.1129T>C)?

AlphaMissense predicts likely benign (score 0.3167) — an in-silico prediction, not a clinical call.

CCDC63 p.Ser377Pro

c.1129T>C · VCV3997108

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3167 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3167	likely benign
REVEL	0.173	moderately benign-leaning
SaProt	LLR -10.67	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.53	GERP -2
Regional constraint	o/e 0.92	unconstrained · MANE · 55 kb · p 0.045 · regional, not allelic
Overall
CADD	13.31	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: CCDC63
Protein: p.Ser377Pro
Coding: c.1129T>C
MANE Select: NM_152591
Type: single nucleotide variant
Location: chr12:110893130 (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-ser377pro (accessed [today's date]).

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