Is CCDC87 p.Leu24Pro (c.71T>C) pathogenic?

CCDC87 p.Leu24Pro (c.71T>C) is classified Uncertain significance in CCDC87 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-22). AlphaMissense: ambiguous (0.4303); Very rare (popmax 0.00141%, nfe).

How common is CCDC87 p.Leu24Pro (c.71T>C) in the general population?

CCDC87 p.Leu24Pro (c.71T>C) is very rare (popmax 0.00141%, nfe) (gnomAD).

What do computational predictors say about CCDC87 p.Leu24Pro (c.71T>C)?

AlphaMissense predicts ambiguous (score 0.4303) — an in-silico prediction, not a clinical call.

CCDC87 p.Leu24Pro

c.71T>C · rs1858402705 · VCV3139516

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4303 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00141%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4303	ambiguous
REVEL	0.261	benign-leaning
SaProt	LLR -5.96	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense 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	24.9	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 0.00141% European (non-Finnish) · 16/1,136,206 alleles

Filtering AF 0.000834% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000675%

Overall 0.00105% 16/1,518,912 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.Leu24Pro
Coding: c.71T>C
MANE Select: NM_018219
dbSNP: rs1858402705
Type: single nucleotide variant
Location: chr11:66592945 (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-leu24pro (accessed [today's date]).

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