Is CCDC186 p.Ala102Ser (c.304G>T) pathogenic?

CCDC186 p.Ala102Ser (c.304G>T) is classified Uncertain significance in CCDC186 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-28). AlphaMissense: likely benign (0.0716); Ultra-rare (popmax 0.0111%, eas); Associated with Inborn genetic diseases.

What condition is associated with CCDC186 p.Ala102Ser (c.304G>T)?

CCDC186 p.Ala102Ser (c.304G>T) is associated with Inborn genetic diseases (ClinVar).

How common is CCDC186 p.Ala102Ser (c.304G>T) in the general population?

CCDC186 p.Ala102Ser (c.304G>T) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

What do computational predictors say about CCDC186 p.Ala102Ser (c.304G>T)?

AlphaMissense predicts likely benign (score 0.0716) — an in-silico prediction, not a clinical call.

CCDC186 p.Ala102Ser

c.304G>T · rs560390918 · VCV3139012

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0716 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0716	likely benign
REVEL	0.022	moderately benign-leaning
SaProt	LLR -4.83	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 -0.21	GERP -4, phastCons 0.08
Regional constraint	o/e 0.88	unconstrained · MANE · 38 kb · p 0.00014 · regional, not allelic
Overall
CADD	0.168	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0111% East Asian · 5/44,860 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.00031% 5/1,613,456 alleles · ultra-rare

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.Ala102Ser
Coding: c.304G>T
MANE Select: NM_018017
dbSNP: rs560390918
Type: single nucleotide variant
Location: chr10:114162965 (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.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
CCDC186 p.Arg269Gly 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-ala102ser (accessed [today's date]).

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