Is OTC p.Glu239Val (c.716A>T) pathogenic?

OTC p.Glu239Val (c.716A>T) is classified Pathogenic in OTC (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely benign (0.2016); Absent from gnomAD v4.1.

How common is OTC p.Glu239Val (c.716A>T) in the general population?

OTC p.Glu239Val (c.716A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about OTC p.Glu239Val (c.716A>T)?

AlphaMissense predicts likely benign (score 0.2016) — an in-silico prediction, not a clinical call.

OTC p.Glu239Val

c.716A>T · rs67283833 · VCV97296

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2016 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2016	likely benign ⚠ discordant with ClinVar
REVEL	0.812	moderately pathogenic-leaning
SaProt	LLR -11.59	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	Δ0.79	donor loss · deltas
Pangolin	Δ0.43	loss · gain 0.04 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 68 kb · p 3.9e-05 · 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

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: OTC
Protein: p.Glu239Val
Coding: c.716A>T
MANE Select: NM_000531
dbSNP: rs67283833
Type: single nucleotide variant
Location: chrX:38408794 (GRCh38)
Structure: AlphaFold pLDDT 91.94 · 4 PDB
Residue 239: an α-helix

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

Similar variants

OTC p.Glu239= Likely pathogenic ★★ same residue
OTC p.Glu239Gln Uncertain significance ★★ ⚠ same residue
OTC p.Glu239Asp Likely pathogenic ★ ⚠ same residue
OTC p.Glu239Gly Pathogenic ⚠ same residue
OTC p.Glu239fs Pathogenic ★ same residue
OTC c.298+2T>G Pathogenic ★★ same type
OTC c.299-1G>A Likely pathogenic ★★ same type
OTC c.386+1G>A Pathogenic ★★ 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/otc-p-glu239val (accessed [today's date]).

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