Is CCDC18 p.Gln534Arg (c.1601A>G) pathogenic?

CCDC18 p.Gln534Arg (c.1601A>G) is classified Uncertain significance in CCDC18 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-26). AlphaMissense: likely benign (0.0906); Ultra-rare (popmax 0.0187%, afr).

How common is CCDC18 p.Gln534Arg (c.1601A>G) in the general population?

CCDC18 p.Gln534Arg (c.1601A>G) is ultra-rare (popmax 0.0187%, afr) (gnomAD).

What do computational predictors say about CCDC18 p.Gln534Arg (c.1601A>G)?

AlphaMissense predicts likely benign (score 0.0906) — an in-silico prediction, not a clinical call.

CCDC18 p.Gln534Arg

c.1601A>G · VCV3828474

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0906 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0906	likely benign
REVEL	0.063	moderately benign-leaning
SaProt	LLR -7.24	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 9	GERP 0.32, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 95 kb · p 0.00026 · regional, not allelic
Overall
CADD	22.0	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 Q533R vs ClinVar Q534R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0187% African / African-American · 14/75,038 alleles

Filtering AF 0.0112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00903%

Overall 0.000992% 16/1,613,656 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0187%	5,360
Admixed American	0.00333%	30,010

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: CCDC18
Protein: p.Gln534Arg
Coding: c.1601A>G
MANE Select: NM_001378204
Type: single nucleotide variant
Location: chr1:93214848 (GRCh38)
Gene constraint: LOEUF 0.901 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.83

Full CCDC18 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC18 p.Gln534Glu Uncertain significance ★ ⚠ same residue
CCDC18 p.Cys430= Benign ★★ same type
CCDC18 p.Leu817= Benign ★★ same type
CCDC18 p.Pro108= Benign ★★ same type
CCDC18 p.Ala1077Val Uncertain significance ★ ⚠ same type
CCDC18 p.Ala1209Gly Uncertain significance ★ ⚠ same type
CCDC18 p.Ala1209Pro Uncertain significance ★ ⚠ same type
CCDC18 p.Ala1287Thr 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/ccdc18-p-gln534arg (accessed [today's date]).

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