Is CCDC30 p.Lys220Glu (c.658A>G) pathogenic?

CCDC30 p.Lys220Glu (c.658A>G) is classified Uncertain significance in CCDC30 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-06). AlphaMissense: likely benign (0.0976); Absent from gnomAD v4.1.

How common is CCDC30 p.Lys220Glu (c.658A>G) in the general population?

CCDC30 p.Lys220Glu (c.658A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCDC30 p.Lys220Glu (c.658A>G)?

AlphaMissense predicts likely benign (score 0.0976) — an in-silico prediction, not a clinical call.

CCDC30 p.Lys220Glu

c.658A>G · VCV3486654

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0976 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0976	likely benign
REVEL	0.062	moderately benign-leaning
SaProt	LLR -7.17	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 5.2	GERP 1.5, phastCons 1
Overall
CADD	21.3	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 K65E vs ClinVar K220E) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CCDC30
Protein: p.Lys220Glu
Coding: c.658A>G
MANE Select: NM_001395517
Type: single nucleotide variant
Location: chr1:42539248 (GRCh38)
Gene constraint: LOEUF 0.91 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.27
Residue 220: the 'disordered' region

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

Similar variants

PPCS p.Asp220= Likely benign ★ same residue
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

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-lys220glu (accessed [today's date]).

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