Is CCDC186 p.Ser256Ter (c.767C>G) pathogenic?

CCDC186 p.Ser256Ter (c.767C>G) is classified Pathogenic in CCDC186 (ClinVar, Single submitter, 2 submitters; last evaluated 2021-03-23). Absent from gnomAD v4.1; Associated with Seizure.

What condition is associated with CCDC186 p.Ser256Ter (c.767C>G)?

CCDC186 p.Ser256Ter (c.767C>G) is associated with Seizure, microcephaly, hypothyroidism (ClinVar).

How common is CCDC186 p.Ser256Ter (c.767C>G) in the general population?

CCDC186 p.Ser256Ter (c.767C>G) is absent from gnomAD v4.1 (gnomAD).

CCDC186 p.Ser256Ter

c.767C>G · rs2119807637 · VCV1120267

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Seizure

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 16
Splicing
SpliceAI	Δ0.23	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 2.1	GERP -0.3, phastCons 1
Overall
CADD	37.0	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

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: CCDC186
Protein: p.Ser256Ter
Coding: c.767C>G
MANE Select: NM_018017
dbSNP: rs2119807637
Type: single nucleotide variant
Location: chr10:114151213 (GRCh38)
Gene constraint: LOEUF 0.56 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 74.62

Full CCDC186 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Also linked: microcephaly hypothyroidism pulmonary valve stenosis

Similar variants

CCDC186 p.Tyr141His Uncertain significance ★★ ⚠ same type
CCDC186 p.Lys482= Benign ★★ same type
CCDC186 p.Ala102Ser Uncertain significance ★ ⚠ same type
CCDC186 p.Ala531Thr Uncertain significance ★ ⚠ same type
CCDC186 p.Ala543Gly Uncertain significance ★ ⚠ same type
CCDC186 p.Ala600Thr Uncertain significance ★ ⚠ same type
CCDC186 p.Ala65Val Uncertain significance ★ ⚠ same type
CCDC186 p.Ala688Ser 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/ccdc186-p-ser256ter (accessed [today's date]).

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