Is CCDC87 p.Leu473Pro (c.1418T>C) pathogenic?

CCDC87 p.Leu473Pro (c.1418T>C) is classified Uncertain significance in CCDC87 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-28). AlphaMissense: likely pathogenic (0.6494); Rare (popmax 0.153%, afr).

How common is CCDC87 p.Leu473Pro (c.1418T>C) in the general population?

CCDC87 p.Leu473Pro (c.1418T>C) is rare (popmax 0.153%, afr) (gnomAD).

What do computational predictors say about CCDC87 p.Leu473Pro (c.1418T>C)?

AlphaMissense predicts likely pathogenic (score 0.6494) — an in-silico prediction, not a clinical call.

CCDC87 p.Leu473Pro

c.1418T>C · rs138056551 · VCV2266714

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6494 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.153%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6494	likely pathogenic · top 9% in CCDC87
REVEL	0.327	indeterminate
SaProt	LLR -6.01	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 2,546 bp · p 0.35 · regional, not allelic
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.153% African / African-American · 115/75,062 alleles

Filtering AF 0.13% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.122%

Overall 0.00799% 129/1,614,154 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.153%	653
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.016%	6,251
Admixed American	0.00167%	60,016
South Asian	0.0011%	91,086
European (non-Finnish)	8.47e-05%	1,180,038

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.Leu473Pro
Coding: c.1418T>C
MANE Select: NM_018219
dbSNP: rs138056551
Type: single nucleotide variant
Location: chr11:66591598 (GRCh38)
Structure: AlphaFold pLDDT 62.53

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

Similar variants

CCDC87 p.Leu473Val Uncertain significance ★ ⚠ same residue
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

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-leu473pro (accessed [today's date]).

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