Is CCDC13 p.Val128Ile (c.382G>A) pathogenic?

CCDC13 p.Val128Ile (c.382G>A) is classified Uncertain significance in CCDC13 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-22). AlphaMissense: likely benign (0.0827); Ultra-rare (popmax 0.045%, amr).

How common is CCDC13 p.Val128Ile (c.382G>A) in the general population?

CCDC13 p.Val128Ile (c.382G>A) is ultra-rare (popmax 0.045%, amr) (gnomAD).

What do computational predictors say about CCDC13 p.Val128Ile (c.382G>A)?

AlphaMissense predicts likely benign (score 0.0827) — an in-silico prediction, not a clinical call.

CCDC13 p.Val128Ile

c.382G>A · rs201462906 · VCV2355946

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0827 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.045%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0827	likely benign
REVEL	0.045	moderately benign-leaning
SaProt	LLR -7.60	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 -5.8	GERP -4
Regional constraint	o/e 0.94	unconstrained · MANE · 49 kb · p 0.094 · regional, not allelic
Overall
CADD	0.038	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 0.045% Admixed American · 27/60,010 alleles

Filtering AF 0.0317% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0273%

Overall 0.0105% 170/1,614,006 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.045%	2,223
Middle Eastern	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.0128%	7,811
European (non-Finnish)	0.0112%	8,940
African / African-American	0.00267%	37,474

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.Val128Ile
Coding: c.382G>A
MANE Select: NM_144719
dbSNP: rs201462906
Type: single nucleotide variant
Location: chr3:42752706 (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.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-val128ile (accessed [today's date]).

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