Is ENDOU p.Leu231Pro (c.692T>C) pathogenic?

ENDOU p.Leu231Pro (c.692T>C) is classified Uncertain significance in ENDOU (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-11). AlphaMissense: likely pathogenic (0.9477); Absent from gnomAD v4.1.

How common is ENDOU p.Leu231Pro (c.692T>C) in the general population?

ENDOU p.Leu231Pro (c.692T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ENDOU p.Leu231Pro (c.692T>C)?

AlphaMissense predicts likely pathogenic (score 0.9477) — an in-silico prediction, not a clinical call.

ENDOU p.Leu231Pro

c.692T>C · VCV3275420

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9477 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9477	likely pathogenic · top 2% in ENDOU
REVEL	0.754	pathogenic-leaning
SaProt	LLR -16.60	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 15 kb · p 0.018 · regional, not allelic
Overall
CADD	28.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ENDOU
Protein: p.Leu231Pro
Coding: c.692T>C
MANE Select: NM_001172439
Type: single nucleotide variant
Location: chr12:47716359 (GRCh38)
Gene constraint: LOEUF 1.094 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.91 · 1 PDB
Residue 231: an α-helix; the endou domain

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

Similar variants

ENDOU p.Arg211Gln Benign ★★ same type
ENDOU p.Asp228= Benign ★★ same type
ENDOU p.Tyr317= Benign ★★ same type
ENDOU c.551+1G>A Uncertain significance ★ same type
ENDOU p.Ala229Val Uncertain significance ★ ⚠ same type
ENDOU p.Ala402Thr Uncertain significance ★ ⚠ same type
ENDOU p.Ala404Pro Uncertain significance ★ ⚠ same type
ENDOU p.Ala78Asp 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/endou-p-leu231pro (accessed [today's date]).

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