Is CCDC18 p.Ser45Arg (c.135T>A) pathogenic?

CCDC18 p.Ser45Arg (c.135T>A) is classified Uncertain significance in CCDC18 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-27). AlphaMissense: ambiguous (0.3438); Absent from gnomAD v4.1.

How common is CCDC18 p.Ser45Arg (c.135T>A) in the general population?

CCDC18 p.Ser45Arg (c.135T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCDC18 p.Ser45Arg (c.135T>A)?

AlphaMissense predicts ambiguous (score 0.3438) — an in-silico prediction, not a clinical call.

CCDC18 p.Ser45Arg

c.135T>A · rs2524313148 · VCV3138910

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3438 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3438	ambiguous
REVEL	0.089	moderately benign-leaning
SaProt	LLR -7.31	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP 0.29, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 95 kb · p 0.00026 · regional, not allelic
Overall
CADD	18.52	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

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: CCDC18
Protein: p.Ser45Arg
Coding: c.135T>A
MANE Select: NM_001378204
dbSNP: rs2524313148
Type: single nucleotide variant
Location: chr1:93183978 (GRCh38)
Gene constraint: LOEUF 0.901 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.83
Residue 45: a modified residue (phosphoserine)

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.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
CCDC18 p.Ala241Thr 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-ser45arg (accessed [today's date]).

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