Is CCDC30 p.Ile511Val (c.1531A>G) pathogenic?

CCDC30 p.Ile511Val (c.1531A>G) is classified Uncertain significance in CCDC30 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-14). AlphaMissense: likely benign (0.1801); Very rare (popmax 0.00136%, afr).

How common is CCDC30 p.Ile511Val (c.1531A>G) in the general population?

CCDC30 p.Ile511Val (c.1531A>G) is very rare (popmax 0.00136%, afr) (gnomAD).

What do computational predictors say about CCDC30 p.Ile511Val (c.1531A>G)?

AlphaMissense predicts likely benign (score 0.1801) — an in-silico prediction, not a clinical call.

CCDC30 p.Ile511Val

c.1531A>G · VCV4221176

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1801 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00136%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1801	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -7.55	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.1	GERP 1.6, phastCons 1
Overall
CADD	19.06	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 I356V vs ClinVar I511V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00136% African / African-American · 1/73,266 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000314% 5/1,593,168 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00136%	73,266
European (non-Finnish)	0.000341%	293,571

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.Ile511Val
Coding: c.1531A>G
MANE Select: NM_001395517
Type: single nucleotide variant
Location: chr1:42581360 (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-ile511val (accessed [today's date]).

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