Is CCDC186 p.Val652Asp (c.1955T>A) pathogenic?

CCDC186 p.Val652Asp (c.1955T>A) is classified Uncertain significance in CCDC186 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-23). AlphaMissense: ambiguous (0.5107); Very rare (popmax 0.00622%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CCDC186 p.Val652Asp (c.1955T>A)?

CCDC186 p.Val652Asp (c.1955T>A) is associated with Inborn genetic diseases (ClinVar).

How common is CCDC186 p.Val652Asp (c.1955T>A) in the general population?

CCDC186 p.Val652Asp (c.1955T>A) is very rare (popmax 0.00622%, nfe) (gnomAD).

What do computational predictors say about CCDC186 p.Val652Asp (c.1955T>A)?

AlphaMissense predicts ambiguous (score 0.5107) — an in-silico prediction, not a clinical call.

CCDC186 p.Val652Asp

c.1955T>A · rs752430429 · VCV2523347

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5107 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00622%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5107	ambiguous
REVEL	0.192	benign-leaning
SaProt	LLR -10.57	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	GERP 2.7, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 38 kb · p 0.00014 · regional, not allelic
Overall
CADD	25.2	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 0.00622% European (non-Finnish) · 73/1,173,392 alleles

Filtering AF 0.00506% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00465%

Overall 0.0047% 75/1,597,286 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00622%	16,074
Remaining individualsnot grpmax-eligible	0.00324%	30,902

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.Val652Asp
Coding: c.1955T>A
MANE Select: NM_018017
dbSNP: rs752430429
Type: single nucleotide variant
Location: chr10:114131293 (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.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
CCDC186 p.Arg257Ile 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-val652asp (accessed [today's date]).

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