Is CCDC13 p.Arg440Pro (c.1319G>C) pathogenic?

CCDC13 p.Arg440Pro (c.1319G>C) is classified Uncertain significance in CCDC13 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-04). AlphaMissense: likely pathogenic (0.9726); Absent from gnomAD v4.1.

How common is CCDC13 p.Arg440Pro (c.1319G>C) in the general population?

CCDC13 p.Arg440Pro (c.1319G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCDC13 p.Arg440Pro (c.1319G>C)?

AlphaMissense predicts likely pathogenic (score 0.9726) — an in-silico prediction, not a clinical call.

CCDC13 p.Arg440Pro

c.1319G>C · VCV3485979

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9726 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9726	likely pathogenic · top 1% in CCDC13
REVEL	0.181	moderately benign-leaning
SaProt	LLR -12.22	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 49 kb · p 0.094 · regional, not allelic
Overall
CADD	27.0	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: CCDC13
Protein: p.Arg440Pro
Coding: c.1319G>C
MANE Select: NM_144719
Type: single nucleotide variant
Location: chr3:42735759 (GRCh38)
Gene constraint: LOEUF 0.906 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.77

Full CCDC13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC13 p.Arg440Gln Uncertain significance ★ ⚠ same residue
CCDC13 p.Glu565Lys Uncertain significance ★★ ⚠ same type
CCDC13 p.Ala129Thr Uncertain significance ★ ⚠ same type
CCDC13 p.Ala175Thr Uncertain significance ★ ⚠ same type
CCDC13 p.Ala187Thr Uncertain significance ★ ⚠ same type
CCDC13 p.Ala332Gly Uncertain significance ★ ⚠ same type
CCDC13 p.Ala3Val Uncertain significance ★ ⚠ same type
CCDC13 p.Ala517Val 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/ccdc13-p-arg440pro (accessed [today's date]).

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