Is ENDOG p.Ala284Val (c.851C>T) pathogenic?

ENDOG p.Ala284Val (c.851C>T) is classified Uncertain significance in ENDOG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-26). AlphaMissense: likely benign (0.1628); Ultra-rare (popmax 0.0167%, mid).

How common is ENDOG p.Ala284Val (c.851C>T) in the general population?

ENDOG p.Ala284Val (c.851C>T) is ultra-rare (popmax 0.0167%, mid) (gnomAD).

What do computational predictors say about ENDOG p.Ala284Val (c.851C>T)?

AlphaMissense predicts likely benign (score 0.1628) — an in-silico prediction, not a clinical call.

ENDOG p.Ala284Val

c.851C>T · VCV3844828

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1628 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1628	likely benign
REVEL	0.109	moderately benign-leaning
SaProt	LLR -10.17	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 3,922 bp · p 0.17 · regional, not allelic
Overall
CADD	24.3	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 0.0167% Middle Eastern · 1/5,998 alleles

Overall 0.000212% 3/1,413,034 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0167%	5,998
Finnishnot grpmax-eligible	0.00166%	60,358
European (non-Finnish)	8.66e-05%	1,154,678

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.Ala284Val
Coding: c.851C>T
MANE Select: NM_004435
Type: single nucleotide variant
Location: chr9:128822567 (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.Arg103His 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-ala284val (accessed [today's date]).

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