Is CCDC86 p.Arg330Trp (c.988C>T) pathogenic?

CCDC86 p.Arg330Trp (c.988C>T) is classified Uncertain significance in CCDC86 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-17). AlphaMissense: likely pathogenic (0.6662); Very rare (popmax 0.00891%, eas).

How common is CCDC86 p.Arg330Trp (c.988C>T) in the general population?

CCDC86 p.Arg330Trp (c.988C>T) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about CCDC86 p.Arg330Trp (c.988C>T)?

AlphaMissense predicts likely pathogenic (score 0.6662) — an in-silico prediction, not a clinical call.

CCDC86 p.Arg330Trp

c.988C>T · rs141710276 · VCV2382740

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6662 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6662	likely pathogenic
REVEL	0.291	indeterminate
SaProt	LLR -13.83	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.31	GERP 1.6, phastCons 0.98
Regional constraint	o/e 0.96	unconstrained · MANE · 8,197 bp · p 0.43 · regional, not allelic
Overall
CADD	27.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00891% East Asian · 4/44,880 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00223% 36/1,614,216 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,220
Remaining individualsnot grpmax-eligible	0.0048%	20,837
Admixed American	0.00333%	30,013
European (non-Finnish)	0.00212%	47,201
African / African-American	0.00133%	75,066
South Asian	0.0011%	91,084

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.Arg330Trp
Coding: c.988C>T
MANE Select: NM_024098
dbSNP: rs141710276
Type: single nucleotide variant
Location: chr11:60850230 (GRCh38)
Gene constraint: LOEUF 1.008 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.88 · 10 PDB
Residue 330: the 'disordered' region; an α-helix

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

Similar variants

CCDC86 p.Arg330Gly Uncertain significance ★ ⚠ same residue
CCDC86 p.Arg330Leu Uncertain significance ★ ⚠ same residue
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

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-arg330trp (accessed [today's date]).

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