Is CCDC186 p.Arg359Trp (c.1075C>T) pathogenic?

CCDC186 p.Arg359Trp (c.1075C>T) is classified Uncertain significance in CCDC186 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-25). AlphaMissense: ambiguous (0.4777); Ultra-rare (popmax 0.0178%, eas); Associated with Inborn genetic diseases.

What condition is associated with CCDC186 p.Arg359Trp (c.1075C>T)?

CCDC186 p.Arg359Trp (c.1075C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CCDC186 p.Arg359Trp (c.1075C>T) in the general population?

CCDC186 p.Arg359Trp (c.1075C>T) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

What do computational predictors say about CCDC186 p.Arg359Trp (c.1075C>T)?

AlphaMissense predicts ambiguous (score 0.4777) — an in-silico prediction, not a clinical call.

CCDC186 p.Arg359Trp

c.1075C>T · VCV3264145

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4777 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4777	ambiguous
REVEL	0.384	indeterminate
SaProt	LLR -10.94	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.2	GERP -0.51, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 38 kb · p 0.00014 · regional, not allelic
Overall
CADD	27.2	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

Grpmax group 0.0178% East Asian · 8/44,836 alleles

Filtering AF 0.00884% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.00286% 46/1,610,382 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0178%	5,605
Admixed American	0.00672%	14,871
South Asian	0.00332%	30,123
European (non-Finnish)	0.00254%	39,316
Remaining individualsnot grpmax-eligible	0.00161%	62,254

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: CCDC186
Protein: p.Arg359Trp
Coding: c.1075C>T
MANE Select: NM_018017
Type: single nucleotide variant
Location: chr10:114145575 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CCDC186 p.Arg359Gln Uncertain significance ★ ⚠ same residue
CCDC186 p.Tyr141His Uncertain significance ★★ ⚠ same condition
CCDC186 p.Ala102Ser Uncertain significance ★ ⚠ same condition
CCDC186 p.Ala531Thr Uncertain significance ★ ⚠ same condition
CCDC186 p.Ala543Gly Uncertain significance ★ ⚠ same condition
CCDC186 p.Ala600Thr Uncertain significance ★ ⚠ same condition
CCDC186 p.Ala65Val Uncertain significance ★ ⚠ same condition
CCDC186 p.Ala688Ser Uncertain significance ★ ⚠ 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/ccdc186-p-arg359trp (accessed [today's date]).

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