Is EOGT p.Pro489Leu (c.1466C>T) pathogenic?

EOGT p.Pro489Leu (c.1466C>T) is classified Uncertain significance in EOGT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-04-08). AlphaMissense: likely benign (0.2354); Ultra-rare (popmax 0.0132%, nfe); Associated with Inborn genetic diseases.

What condition is associated with EOGT p.Pro489Leu (c.1466C>T)?

EOGT p.Pro489Leu (c.1466C>T) is associated with Inborn genetic diseases (ClinVar).

How common is EOGT p.Pro489Leu (c.1466C>T) in the general population?

EOGT p.Pro489Leu (c.1466C>T) is ultra-rare (popmax 0.0132%, nfe) (gnomAD).

What do computational predictors say about EOGT p.Pro489Leu (c.1466C>T)?

AlphaMissense predicts likely benign (score 0.2354) — an in-silico prediction, not a clinical call.

EOGT p.Pro489Leu

c.1466C>T · rs199832969 · VCV2391778

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2354 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0132%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2354	likely benign
REVEL	0.18	moderately benign-leaning
SaProt	LLR -13.30	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 8.5	GERP 1.2, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 32 kb · p 0.016 · regional, not allelic
Overall
CADD	24.8	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 0.0132% European (non-Finnish) · 156/1,179,662 alleles

Filtering AF 0.0115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0108%

Overall 0.01% 162/1,613,112 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0132%	7,562
Remaining individualsnot grpmax-eligible	0.0048%	20,817
Finnishnot grpmax-eligible	0.00313%	31,999
East Asian	0.00223%	44,788

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: EOGT
Protein: p.Pro489Leu
Coding: c.1466C>T
MANE Select: NM_001278689
dbSNP: rs199832969
Type: single nucleotide variant
Location: chr3:68977736 (GRCh38)
Gene constraint: LOEUF 1.121 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.71

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EOGT p.Pro489= Likely benign ★ same residue
EOGT p.Arg149His Uncertain significance ★★ ⚠ same condition
EOGT p.Arg377Trp Uncertain significance ★★ ⚠ same condition
EOGT p.Arg452His Uncertain significance ★★ ⚠ same condition
EOGT p.Arg470Trp Uncertain significance ★★ ⚠ same condition
EOGT p.Asp525Glu Uncertain significance ★★ ⚠ same condition
EOGT p.Glu487Gly Uncertain significance ★★ ⚠ same condition
EOGT p.His481Arg Uncertain significance ★★ ⚠ same condition

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/eogt-p-pro489leu (accessed [today's date]).

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