Is CCDC30 p.Arg673His (c.2018G>A) pathogenic?

CCDC30 p.Arg673His (c.2018G>A) is classified Uncertain significance in CCDC30 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-26). AlphaMissense: likely benign (0.0897); Ultra-rare (popmax 0.0292%, eas).

How common is CCDC30 p.Arg673His (c.2018G>A) in the general population?

CCDC30 p.Arg673His (c.2018G>A) is ultra-rare (popmax 0.0292%, eas) (gnomAD).

What do computational predictors say about CCDC30 p.Arg673His (c.2018G>A)?

AlphaMissense predicts likely benign (score 0.0897) — an in-silico prediction, not a clinical call.

CCDC30 p.Arg673His

c.2018G>A · VCV3486648

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0897 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0292%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0897	likely benign
REVEL	0.002	strongly benign-leaning
SaProt	LLR -6.50	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	GERP -4.5
Overall
CADD	0.82	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 R518H vs ClinVar R673H) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0292% East Asian · 13/44,520 alleles

Filtering AF 0.0172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0137%

Overall 0.00638% 101/1,582,386 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0292%	3,425
Remaining individualsnot grpmax-eligible	0.0245%	4,080
African / African-American	0.0138%	7,258
South Asian	0.00705%	14,190
European (non-Finnish)	0.00461%	21,691
Admixed American	0.00411%	24,330
Ashkenazi Jewishnot grpmax-eligible	0.00353%	28,322

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.Arg673His
Coding: c.2018G>A
MANE Select: NM_001395517
Type: single nucleotide variant
Location: chr1:42637293 (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

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PPCS p.Arg263Gln Uncertain significance ★★ ⚠ same type
PPCS p.Leu74Pro Uncertain significance ★★ ⚠ same type
PPCS p.Leu83Ter Uncertain significance ★★ same type
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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-arg673his (accessed [today's date]).

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