Is OTC p.Ile172Phe (c.514A>T) pathogenic?

OTC p.Ile172Phe (c.514A>T) is classified Pathogenic in OTC (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely pathogenic (0.8613); Absent from gnomAD v4.1.

How common is OTC p.Ile172Phe (c.514A>T) in the general population?

OTC p.Ile172Phe (c.514A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about OTC p.Ile172Phe (c.514A>T)?

AlphaMissense predicts likely pathogenic (score 0.8613) — an in-silico prediction, not a clinical call.

OTC p.Ile172Phe

c.514A>T · rs72556279 · VCV97229

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8613 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8613	likely pathogenic ✓ concordant with ClinVar
REVEL	0.952	strongly pathogenic-leaning
SaProt	LLR -11.64	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.4, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 68 kb · p 3.9e-05 · regional, not allelic
Overall
CADD	26.1	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.Ile172Phe
Coding: c.514A>T
MANE Select: NM_000531
dbSNP: rs72556279
Type: single nucleotide variant
Location: chrX:38401402 (GRCh38)
Structure: AlphaFold pLDDT 91.94 · 4 PDB
Residue 172: an α-helix; a UniProt-annotated variant site (in otcd); a UniProt-annotated variant site (in otcd; early onset; loss of ornithine carbamoyltransferase activity)

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

Similar variants

OTC p.Ile172= Likely benign ★ same residue
OTC p.Ile172Met 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
OTC c.540+1G>A Pathogenic ★★ same type
OTC c.540+1G>T Pathogenic ★★ same type
OTC c.540+265G>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-ile172phe (accessed [today's date]).

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