Is CCDC183 p.Trp342Ter (c.1025G>A) pathogenic?

CCDC183 p.Trp342Ter (c.1025G>A) is classified Likely pathogenic in CCDC183 (ClinVar, No assertion criteria, 1 submitter). Ultra-rare (popmax 0.0438%, afr); Associated with essential tremor.

What condition is associated with CCDC183 p.Trp342Ter (c.1025G>A)?

CCDC183 p.Trp342Ter (c.1025G>A) is associated with essential tremor (ClinVar).

How common is CCDC183 p.Trp342Ter (c.1025G>A) in the general population?

CCDC183 p.Trp342Ter (c.1025G>A) is ultra-rare (popmax 0.0438%, afr) (gnomAD).

CCDC183 p.Trp342Ter

c.1025G>A · rs749875462 · VCV1184863

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0438%, afr)

Conditions

essential tremor

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 10 of 14
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.95	GERP 0.38, phastCons 0.001
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0438% African / African-American · 32/73,048 alleles

Filtering AF 0.0318% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0278%

Overall 0.00684% 106/1,550,380 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0438%	2,283
Remaining individualsnot grpmax-eligible	0.00833%	12,010
European (non-Finnish)	0.00558%	17,917
Admixed American	0.00392%	25,533
East Asian	0.00244%	40,992
South Asian	0.00238%	42,034

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: CCDC183
Protein: p.Trp342Ter
Coding: c.1025G>A
MANE Select: NM_001039374
dbSNP: rs749875462
Type: single nucleotide variant
Location: chr9:136806154 (GRCh38)
Gene constraint: LOEUF 1.225 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.98
Residue 342: a UniProt-annotated variant site (in)

Full CCDC183 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

essential tremor — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CCDC183 p.Gln296Ter Likely pathogenic ★ same type
CCDC183 p.Ala238Thr Uncertain significance ★ ⚠ same type
CCDC183 p.Ala348Thr Uncertain significance ★ ⚠ same type
CCDC183 p.Ala392Val Uncertain significance ★ ⚠ same type
CCDC183 p.Ala424Glu Uncertain significance ★ ⚠ same type
CCDC183 p.Ala518Thr Uncertain significance ★ ⚠ same type
CCDC183 p.Arg117Pro Uncertain significance ★ ⚠ same type
CCDC183 p.Arg132Gly 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/ccdc183-p-trp342ter (accessed [today's date]).

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