Is CCDC86 p.Pro16Leu (c.47C>T) pathogenic?

CCDC86 p.Pro16Leu (c.47C>T) is classified Uncertain significance in CCDC86 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-17). AlphaMissense: likely benign (0.1221); Ultra-rare (popmax 0.0451%, sas).

How common is CCDC86 p.Pro16Leu (c.47C>T) in the general population?

CCDC86 p.Pro16Leu (c.47C>T) is ultra-rare (popmax 0.0451%, sas) (gnomAD).

What do computational predictors say about CCDC86 p.Pro16Leu (c.47C>T)?

AlphaMissense predicts likely benign (score 0.1221) — an in-silico prediction, not a clinical call.

CCDC86 p.Pro16Leu

c.47C>T · rs750060598 · VCV2404772

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1221 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0451%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1221	likely benign
REVEL	0.164	moderately benign-leaning
SaProt	LLR -6.88	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 2.5	GERP 1.6, phastCons 0.91
Regional constraint	o/e 0.96	unconstrained · MANE · 8,197 bp · p 0.43 · regional, not allelic
Overall
CADD	22.2	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 0.0451% South Asian · 41/90,846 alleles

Filtering AF 0.0341% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0303%

Overall 0.00615% 99/1,609,540 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0451%	2,216
Middle Eastern	0.0332%	3,015
Admixed American	0.0186%	5,369
European (non-Finnish)	0.00365%	27,404
Remaining individualsnot grpmax-eligible	0.00321%	31,109

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: CCDC86
Protein: p.Pro16Leu
Coding: c.47C>T
MANE Select: NM_024098
dbSNP: rs750060598
Type: single nucleotide variant
Location: chr11:60842171 (GRCh38)
Gene constraint: LOEUF 1.008 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.88 · 10 PDB
Residue 16: the 'disordered' region

Full CCDC86 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC86 p.Ala139Thr Uncertain significance ★ ⚠ same type
CCDC86 p.Ala139Val Uncertain significance ★ ⚠ same type
CCDC86 p.Ala149Gly Uncertain significance ★ ⚠ same type
CCDC86 p.Ala149Thr Uncertain significance ★ ⚠ same type
CCDC86 p.Ala169Gly Uncertain significance ★ ⚠ same type
CCDC86 p.Ala169Pro Uncertain significance ★ ⚠ same type
CCDC86 p.Ala358Pro Uncertain significance ★ ⚠ same type
CCDC86 p.Ala89Thr 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/ccdc86-p-pro16leu (accessed [today's date]).

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