Is ENDOG p.Pro87Leu (c.260C>T) pathogenic?

ENDOG p.Pro87Leu (c.260C>T) is classified Uncertain significance in ENDOG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-02). AlphaMissense: ambiguous (0.4198); Very rare (popmax 0.00219%, amr).

How common is ENDOG p.Pro87Leu (c.260C>T) in the general population?

ENDOG p.Pro87Leu (c.260C>T) is very rare (popmax 0.00219%, amr) (gnomAD).

What do computational predictors say about ENDOG p.Pro87Leu (c.260C>T)?

AlphaMissense predicts ambiguous (score 0.4198) — an in-silico prediction, not a clinical call.

ENDOG p.Pro87Leu

c.260C>T · VCV4017966

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4198 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00219%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4198	ambiguous
REVEL	0.2	benign-leaning
SaProt	LLR -8.57	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 7.3	GERP 1.2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 3,922 bp · p 0.17 · regional, not allelic
Overall
CADD	26.1	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 0.00219% Admixed American · 1/45,574 alleles

Overall 7.46e-05% 1/1,340,484 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: ENDOG
Protein: p.Pro87Leu
Coding: c.260C>T
MANE Select: NM_004435
Type: single nucleotide variant
Location: chr9:128818944 (GRCh38)
Gene constraint: LOEUF 1.847 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.67 · 2 PDB

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

Similar variants

ENDOG p.Arg184Cys Uncertain significance ★★ ⚠ same type
ENDOG p.Ile218= Benign ★★ same type
ENDOG p.Thr246Ile Benign ★★ ⚠ same type
ENDOG p.Ala130Val Uncertain significance ★ ⚠ same type
ENDOG p.Ala143Asp Uncertain significance ★ ⚠ same type
ENDOG p.Ala14Val Uncertain significance ★ ⚠ same type
ENDOG p.Ala252Val Uncertain significance ★ ⚠ same type
ENDOG p.Ala284Val 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/endog-p-pro87leu (accessed [today's date]).

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