Is CCDC18 p.Pro108= (c.324T>C) pathogenic?

CCDC18 p.Pro108= (c.324T>C) is classified Benign in CCDC18 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2019-12-31). Common (popmax 5.27%, afr) — too common for a highly-penetrant pathogenic allele.

CCDC18 p.Pro108=

Q: How common is CCDC18 p.Pro108= (c.324T>C) in the general population?

CCDC18 p.Pro108= (c.324T>C) is common (popmax 5.27%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.324T>C · rs74596359 · VCV783939

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 5.27%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.01	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.35	GERP -2.5, phastCons 0.006
Overall
CADD	3.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.27% African / African-American · 3,946/74,904 alleles

Filtering AF 5.13% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.07%

Overall 0.278% 4,486/1,610,980 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.27%	19
Remaining individualsnot grpmax-eligible	0.305%	328
Admixed American	0.26%	385
Middle Eastern	0.133%	754
European (non-Finnish)	0.0154%	6,475
South Asian	0.00553%	18,070

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.Pro108=
Coding: c.324T>C
MANE Select: NM_001378204
dbSNP: rs74596359
Type: single nucleotide variant
Location: chr1:93186365 (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.Cys430= Benign ★★ same type
CCDC18 p.Leu817= 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
CCDC18 p.Ala241Thr Uncertain significance ★ ⚠ same type
CCDC18 p.Ala373Ser 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-pro108 (accessed [today's date]).

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