Is CCDC30 p.Ala448Val (c.1343C>T) pathogenic?

CCDC30 p.Ala448Val (c.1343C>T) is classified Uncertain significance in CCDC30 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-11). AlphaMissense: likely benign (0.1411); Very rare (popmax 0.00017%, nfe).

How common is CCDC30 p.Ala448Val (c.1343C>T) in the general population?

CCDC30 p.Ala448Val (c.1343C>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about CCDC30 p.Ala448Val (c.1343C>T)?

AlphaMissense predicts likely benign (score 0.1411) — an in-silico prediction, not a clinical call.

CCDC30 p.Ala448Val

c.1343C>T · VCV4221181

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1411 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1411	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -5.33	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 4.7	GERP 1.5, phastCons 1
Overall
CADD	22.5	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A293V vs ClinVar A448V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,272 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,460,806 alleles · very rare

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: CCDC30
Protein: p.Ala448Val
Coding: c.1343C>T
MANE Select: NM_001395517
Type: single nucleotide variant
Location: chr1:42577042 (GRCh38)
Gene constraint: LOEUF 0.91 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.27

Full CCDC30 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PPCS p.Glu233Val Pathogenic/Likely pathogenic ★★ same type
PPCS p.Ala237Thr Uncertain significance ★★ ⚠ same type
PPCS p.Ala70Thr Uncertain significance ★★ ⚠ same type
PPCS p.Arg263Gln Uncertain significance ★★ ⚠ same type
PPCS p.Leu74Pro Uncertain significance ★★ ⚠ same type
PPCS p.Leu83Ter Uncertain significance ★★ same type
PPCS p.Met4Thr Uncertain significance ★★ ⚠ same type
PPCS p.Pro6Leu 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/ccdc30-p-ala448val (accessed [today's date]).

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