Is CCDC13 p.Leu40Phe (c.118C>T) pathogenic?

CCDC13 p.Leu40Phe (c.118C>T) is classified Uncertain significance in CCDC13 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-23). AlphaMissense: likely benign (0.078); Very rare (popmax 0.00161%, nfe).

How common is CCDC13 p.Leu40Phe (c.118C>T) in the general population?

CCDC13 p.Leu40Phe (c.118C>T) is very rare (popmax 0.00161%, nfe) (gnomAD).

What do computational predictors say about CCDC13 p.Leu40Phe (c.118C>T)?

AlphaMissense predicts likely benign (score 0.078) — an in-silico prediction, not a clinical call.

CCDC13 p.Leu40Phe

c.118C>T · rs778360015 · VCV2528830

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.078 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00161%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.078	likely benign
REVEL	0.099	moderately benign-leaning
SaProt	LLR -8.36	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 1.5	GERP -0.81, phastCons 0.55
Regional constraint	o/e 0.94	unconstrained · MANE · 49 kb · p 0.094 · regional, not allelic
Overall
CADD	12.29	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

Grpmax group 0.00161% European (non-Finnish) · 19/1,180,030 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.00137% 20/1,461,738 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00161%	62,107
Remaining individualsnot grpmax-eligible	0.0016%	62,488

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CCDC13
Protein: p.Leu40Phe
Coding: c.118C>T
MANE Select: NM_144719
dbSNP: rs778360015
Type: single nucleotide variant
Location: chr3:42758228 (GRCh38)
Gene constraint: LOEUF 0.906 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.77
Residue 40: 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-leu40phe (accessed [today's date]).

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