Is CCDC18 p.Asp1269Glu (c.3807T>A) pathogenic?

CCDC18 p.Asp1269Glu (c.3807T>A) is classified Benign in CCDC18 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-28). AlphaMissense: likely benign (0.1876); Rare (popmax 0.701%, afr); Associated with CCDC18-related disorder.

What condition is associated with CCDC18 p.Asp1269Glu (c.3807T>A)?

CCDC18 p.Asp1269Glu (c.3807T>A) is associated with CCDC18-related disorder (ClinVar).

How common is CCDC18 p.Asp1269Glu (c.3807T>A) in the general population?

CCDC18 p.Asp1269Glu (c.3807T>A) is rare (popmax 0.701%, afr) (gnomAD).

What do computational predictors say about CCDC18 p.Asp1269Glu (c.3807T>A)?

AlphaMissense predicts likely benign (score 0.1876) — an in-silico prediction, not a clinical call.

CCDC18 p.Asp1269Glu

c.3807T>A · rs139422966 · VCV3040891

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1876 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.701%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CCDC18-related disorder

Computational evidence

Protein change
AlphaMissense	0.1876	likely benign
REVEL	0.125	moderately benign-leaning
SaProt	LLR -4.82	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 0.36	GERP -1.3, phastCons 0.99
Regional constraint	o/e 0.91	unconstrained · MANE · 95 kb · p 0.00026 · regional, not allelic
Overall
CADD	14.73	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM D1268E vs ClinVar D1269E) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.701% African / African-American · 526/75,038 alleles

Filtering AF 0.651% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.632%

Overall 0.0372% 600/1,613,582 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.701%	143
Middle Eastern	0.066%	1,514
Remaining individualsnot grpmax-eligible	0.0528%	1,893
Admixed American	0.0433%	2,308
South Asian	0.00659%	15,177
European (non-Finnish)	0.000424%	235,925

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.Asp1269Glu
Coding: c.3807T>A
MANE Select: NM_001378204
dbSNP: rs139422966
Type: single nucleotide variant
Location: chr1:93264823 (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-asp1269glu (accessed [today's date]).

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