Is CCDC13 p.Lys540Glu (c.1618A>G) pathogenic?

CCDC13 p.Lys540Glu (c.1618A>G) is classified Uncertain significance in CCDC13 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-23). AlphaMissense: likely benign (0.0893); Absent from gnomAD v4.1.

How common is CCDC13 p.Lys540Glu (c.1618A>G) in the general population?

CCDC13 p.Lys540Glu (c.1618A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCDC13 p.Lys540Glu (c.1618A>G)?

AlphaMissense predicts likely benign (score 0.0893) — an in-silico prediction, not a clinical call.

CCDC13 p.Lys540Glu

c.1618A>G · VCV4220427

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0893 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0893	likely benign
REVEL	0.105	moderately benign-leaning
SaProt	LLR -6.50	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.46	acceptor gain, 22 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 5	GERP 0.83, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 49 kb · p 0.094 · regional, not allelic
Overall
CADD	20.9	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: CCDC13
Protein: p.Lys540Glu
Coding: c.1618A>G
MANE Select: NM_144719
Type: single nucleotide variant
Location: chr3:42730567 (GRCh38)
Gene constraint: LOEUF 0.906 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.77
Residue 540: the 'disordered' region

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

Similar variants

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
CCDC13 p.Ala544Thr 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-lys540glu (accessed [today's date]).

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