Is CCDC18 p.Glu2Val (c.5A>T) pathogenic?

CCDC18 p.Glu2Val (c.5A>T) is classified Uncertain significance in CCDC18 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-24). AlphaMissense: likely benign (0.1822); Absent from gnomAD v4.1.

How common is CCDC18 p.Glu2Val (c.5A>T) in the general population?

CCDC18 p.Glu2Val (c.5A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCDC18 p.Glu2Val (c.5A>T)?

AlphaMissense predicts likely benign (score 0.1822) — an in-silico prediction, not a clinical call.

CCDC18 p.Glu2Val

c.5A>T · VCV4220944

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1822 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,549,342)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1822	likely benign
REVEL	0.247	benign-leaning
SaProt	LLR -7.68	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.20	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 6	GERP 0.17, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 95 kb · p 0.00026 · regional, not allelic
Overall
CADD	24.9	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.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,549,342). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CCDC18
Protein: p.Glu2Val
Coding: c.5A>T
MANE Select: NM_001378204
Type: single nucleotide variant
Location: chr1:93183366 (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.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-glu2val (accessed [today's date]).

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