Is CCDC18 p.Pro490His (c.1469C>A) pathogenic?

CCDC18 p.Pro490His (c.1469C>A) is classified Likely benign in CCDC18 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2020-05-21). AlphaMissense: likely benign (0.2835); Rare (popmax 0.289%, nfe); Associated with CCDC18-related disorder.

What condition is associated with CCDC18 p.Pro490His (c.1469C>A)?

CCDC18 p.Pro490His (c.1469C>A) is associated with CCDC18-related disorder (ClinVar).

How common is CCDC18 p.Pro490His (c.1469C>A) in the general population?

CCDC18 p.Pro490His (c.1469C>A) is rare (popmax 0.289%, nfe) (gnomAD).

What do computational predictors say about CCDC18 p.Pro490His (c.1469C>A)?

AlphaMissense predicts likely benign (score 0.2835) — an in-silico prediction, not a clinical call.

CCDC18 p.Pro490His

c.1469C>A · rs200273930 · VCV3053028

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2835 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.289%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CCDC18-related disorder

Computational evidence

Protein change
AlphaMissense	0.2835	likely benign
REVEL	0.253	benign-leaning
SaProt	LLR -6.30	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 7.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 95 kb · p 0.00026 · regional, not allelic
Overall
CADD	25.4	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.289% European (non-Finnish) · 3,393/1,174,452 alleles

Filtering AF 0.281% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.277%

Overall 0.239% 3,830/1,599,328 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.422%	237
European (non-Finnish)grpmax	0.289%	346
Remaining individualsnot grpmax-eligible	0.163%	613
African / African-American	0.0511%	1,957
Admixed American	0.049%	2,040
South Asian	0.00115%	87,130

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro490His
Coding: c.1469C>A
MANE Select: NM_001378204
dbSNP: rs200273930
Type: single nucleotide variant
Location: chr1:93212235 (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

Disease context

CCDC18-related disorder

Similar variants

CCDC18 c.2982-6T>C Likely benign same condition
CCDC18 c.569+9A>G Benign same condition
CCDC18 p.Ala153= Likely benign same condition
CCDC18 p.Arg1108= Benign same condition
CCDC18 p.Arg1108Ser Benign same condition
CCDC18 p.Arg1281= Benign same condition
CCDC18 p.Arg429Cys Benign same condition
CCDC18 p.Asn314= Benign same condition

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-pro490his (accessed [today's date]).

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