Is CCDC30 p.Ala602Pro (c.1804G>C) pathogenic?

CCDC30 p.Ala602Pro (c.1804G>C) is classified Uncertain significance in CCDC30 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-04). AlphaMissense: likely pathogenic (0.7086); Very rare (popmax 0.00203%, nfe).

How common is CCDC30 p.Ala602Pro (c.1804G>C) in the general population?

CCDC30 p.Ala602Pro (c.1804G>C) is very rare (popmax 0.00203%, nfe) (gnomAD).

What do computational predictors say about CCDC30 p.Ala602Pro (c.1804G>C)?

AlphaMissense predicts likely pathogenic (score 0.7086) — an in-silico prediction, not a clinical call.

CCDC30 p.Ala602Pro

c.1804G>C · VCV4221167

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7086 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00203%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7086	likely pathogenic · top 3% in CCDC30
REVEL	0.177	moderately benign-leaning
SaProt	LLR -9.64	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.94	GERP -4.3, phastCons 0.14
Overall
CADD	21.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A447P vs ClinVar A602P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00203% European (non-Finnish) · 24/1,179,892 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00161% 26/1,613,772 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00203%	49,162
Remaining individualsnot grpmax-eligible	0.0016%	62,468
African / African-American	0.00134%	74,886

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.Ala602Pro
Coding: c.1804G>C
MANE Select: NM_001395517
Type: single nucleotide variant
Location: chr1:42589439 (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-ala602pro (accessed [today's date]).

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