Is OGT p.Ala494Pro (c.1480G>C) pathogenic?

OGT p.Ala494Pro (c.1480G>C) is classified Uncertain significance in OGT (ClinVar, Single submitter, 1 submitter; last evaluated 2020-03-14). AlphaMissense: likely pathogenic (0.9975); Absent from gnomAD v4.1; Associated with intellectual disability.

What condition is associated with OGT p.Ala494Pro (c.1480G>C)?

OGT p.Ala494Pro (c.1480G>C) is associated with intellectual disability (ClinVar).

How common is OGT p.Ala494Pro (c.1480G>C) in the general population?

OGT p.Ala494Pro (c.1480G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about OGT p.Ala494Pro (c.1480G>C)?

AlphaMissense predicts likely pathogenic (score 0.9975) — an in-silico prediction, not a clinical call.

OGT p.Ala494Pro

c.1480G>C · VCV4074967

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9975 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability

Computational evidence

Protein change
AlphaMissense	0.9975	likely pathogenic
REVEL	0.247	benign-leaning
SaProt	LLR -14.00	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.24	constrained · MANE · 15 kb · p 7.2e-55 · regional, not allelic
Overall
CADD	26.6	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

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: OGT
Protein: p.Ala494Pro
Coding: c.1480G>C
MANE Select: NM_181672
Type: single nucleotide variant
Location: chrX:71557550 (GRCh38)
Structure: AlphaFold pLDDT 93.41 · 44 PDB
Residue 494: an α-helix

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

Disease context

intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

OGT p.Ala494Val Uncertain significance ★ ⚠ same residue
OGT p.Ala765Thr Uncertain significance ★★ ⚠ same condition
OGT c.2437-7G>C Likely benign ★ same condition
OGT p.Thr932Ile Likely pathogenic ★★ same type
OGT p.Arg117Cys Uncertain significance ★★ same type
OGT p.Arg485Gln Uncertain significance ★★ ⚠ same type
OGT p.Arg555Trp Uncertain significance ★★ ⚠ same type
OGT p.Arg627Cys 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/ogt-p-ala494pro (accessed [today's date]).

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