Is ENDOG p.Arg285Trp (c.853C>T) pathogenic?

ENDOG p.Arg285Trp (c.853C>T) is classified Uncertain significance in ENDOG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-26). AlphaMissense: ambiguous (0.3532); Very rare (popmax 0.00588%, sas).

How common is ENDOG p.Arg285Trp (c.853C>T) in the general population?

ENDOG p.Arg285Trp (c.853C>T) is very rare (popmax 0.00588%, sas) (gnomAD).

What do computational predictors say about ENDOG p.Arg285Trp (c.853C>T)?

AlphaMissense predicts ambiguous (score 0.3532) — an in-silico prediction, not a clinical call.

ENDOG p.Arg285Trp

c.853C>T · VCV4664282

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3532 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00588%, sas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3532	ambiguous
REVEL	0.267	benign-leaning
SaProt	LLR -10.71	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.27	GERP -3.3, phastCons 0.008
Regional constraint	o/e 0.93	unconstrained · MANE · 3,922 bp · p 0.17 · regional, not allelic
Overall
CADD	25.3	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 0.00588% South Asian · 5/85,104 alleles

Filtering AF 0.00222% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00145%

Overall 0.00243% 38/1,565,928 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00588%	17,021
African / African-American	0.00405%	24,689
European (non-Finnish)	0.00242%	41,257
East Asian	0.00233%	42,876
Remaining individualsnot grpmax-eligible	0.00165%	60,698

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.Arg285Trp
Coding: c.853C>T
MANE Select: NM_004435
Type: single nucleotide variant
Location: chr9:128822569 (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.Arg285Gln Uncertain significance ★ ⚠ same residue
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

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-arg285trp (accessed [today's date]).

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