Is ENDOU p.Ala78Val (c.233C>T) pathogenic?

ENDOU p.Ala78Val (c.233C>T) is classified Uncertain significance in ENDOU (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-13). AlphaMissense: likely benign (0.0756); Ultra-rare (popmax 0.022%, amr).

How common is ENDOU p.Ala78Val (c.233C>T) in the general population?

ENDOU p.Ala78Val (c.233C>T) is ultra-rare (popmax 0.022%, amr) (gnomAD).

What do computational predictors say about ENDOU p.Ala78Val (c.233C>T)?

AlphaMissense predicts likely benign (score 0.0756) — an in-silico prediction, not a clinical call.

ENDOU p.Ala78Val

c.233C>T · VCV4017973

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0756 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.022%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0756	likely benign
REVEL	0.022	moderately benign-leaning
SaProt	LLR -6.18	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 0.75	GERP 0.91, phastCons 0.001
Regional constraint	o/e 0.90	unconstrained · MANE · 15 kb · p 0.018 · regional, not allelic
Overall
CADD	13.75	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 0.022% Admixed American · 12/54,484 alleles

Filtering AF 0.0127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00993%

Overall 0.000762% 12/1,575,480 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: ENDOU
Protein: p.Ala78Val
Coding: c.233C>T
MANE Select: NM_001172439
Type: single nucleotide variant
Location: chr12:47718140 (GRCh38)
Gene constraint: LOEUF 1.094 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.91 · 1 PDB

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

Similar variants

ENDOU p.Ala78Asp Uncertain significance ★ ⚠ same residue
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

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-ala78val (accessed [today's date]).

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