Is CCDC87 p.Met283Leu (c.847A>C) pathogenic?

CCDC87 p.Met283Leu (c.847A>C) is classified Uncertain significance in CCDC87 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-22). AlphaMissense: likely benign (0.1156); Ultra-rare (popmax 0.0175%, afr).

How common is CCDC87 p.Met283Leu (c.847A>C) in the general population?

CCDC87 p.Met283Leu (c.847A>C) is ultra-rare (popmax 0.0175%, afr) (gnomAD).

What do computational predictors say about CCDC87 p.Met283Leu (c.847A>C)?

AlphaMissense predicts likely benign (score 0.1156) — an in-silico prediction, not a clinical call.

CCDC87 p.Met283Leu

c.847A>C · VCV4649767

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1156 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0175%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1156	likely benign
REVEL	0.009	strongly benign-leaning
SaProt	LLR -4.96	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 -0.054	GERP -4.5
Regional constraint	o/e 1.03	unconstrained · MANE · 2,546 bp · p 0.35 · regional, not allelic
Overall
CADD	0.206	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 0.0175% African / African-American · 13/74,364 alleles

Filtering AF 0.0103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00818%

Overall 0.000817% 13/1,591,780 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: CCDC87
Protein: p.Met283Leu
Coding: c.847A>C
MANE Select: NM_018219
Type: single nucleotide variant
Location: chr11:66592169 (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-met283leu (accessed [today's date]).

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