Is CCDC87 p.Val798Leu (c.2392G>C) pathogenic?

CCDC87 p.Val798Leu (c.2392G>C) is classified Uncertain significance in CCDC87 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-24). AlphaMissense: likely benign (0.3298); Very rare (popmax 0.000339%, nfe).

How common is CCDC87 p.Val798Leu (c.2392G>C) in the general population?

CCDC87 p.Val798Leu (c.2392G>C) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about CCDC87 p.Val798Leu (c.2392G>C)?

AlphaMissense predicts likely benign (score 0.3298) — an in-silico prediction, not a clinical call.

CCDC87 p.Val798Leu

c.2392G>C · VCV3828855

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3298 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3298	likely benign
REVEL	0.065	moderately benign-leaning
SaProt	LLR -7.59	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 3.3	GERP 1.4, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 2,546 bp · p 0.35 · regional, not allelic
Overall
CADD	22.6	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 0.000339% European (non-Finnish) · 4/1,180,046 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000274% 4/1,461,868 alleles · very 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: CCDC87
Protein: p.Val798Leu
Coding: c.2392G>C
MANE Select: NM_018219
Type: single nucleotide variant
Location: chr11:66590624 (GRCh38)
Structure: AlphaFold pLDDT 62.53

Full CCDC87 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC87 p.Ala118Val Uncertain significance ★ ⚠ same type
CCDC87 p.Ala181Val Uncertain significance ★ ⚠ same type
CCDC87 p.Ala201Ser Uncertain significance ★ ⚠ same type
CCDC87 p.Ala201Val Uncertain significance ★ ⚠ same type
CCDC87 p.Ala322Glu Uncertain significance ★ ⚠ same type
CCDC87 p.Ala390Thr Uncertain significance ★ ⚠ same type
CCDC87 p.Ala530Val Uncertain significance ★ ⚠ same type
CCDC87 p.Ala626Thr 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/ccdc87-p-val798leu (accessed [today's date]).

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