Is OAT p.Arg426Ter (c.1276C>T) pathogenic?

OAT p.Arg426Ter (c.1276C>T) is classified Pathogenic in OAT (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-12-10). Very rare (popmax 0.00668%, eas); Associated with Hyperornithinemia.

What condition is associated with OAT p.Arg426Ter (c.1276C>T)?

OAT p.Arg426Ter (c.1276C>T) is associated with Hyperornithinemia, ornithine aminotransferase deficiency (ClinVar).

How common is OAT p.Arg426Ter (c.1276C>T) in the general population?

OAT p.Arg426Ter (c.1276C>T) is very rare (popmax 0.00668%, eas) (gnomAD).

OAT p.Arg426Ter

c.1276C>T · rs121965058 · VCV177

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Conditions

Hyperornithinemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (10 of 10) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.46	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 9.5	GERP 2, phastCons 1
Overall
CADD	40.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% East Asian · 3/44,886 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000558% 9/1,613,888 alleles · very rare exomes 9/1,461,636 · genomes 0/152,252 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,962
Admixed American	0.00167%	60,008
Remaining individualsnot grpmax-eligible	0.0016%	62,486
South Asian	0.0011%	91,072
European (non-Finnish)	0.000254%	393,295

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: OAT
Protein: p.Arg426Ter
Coding: c.1276C>T
MANE Select: NM_000274
dbSNP: rs121965058
Type: single nucleotide variant
Location: chr10:124397986 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.29 · 35 PDB
Residue 426: an α-helix

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

Disease context

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

Also linked: ornithine aminotransferase deficiency

Similar variants

OAT p.Arg426= Likely benign ★ same residue
OAT p.Arg426Gln Likely benign ★ same residue
OAT c.1014+1G>A Likely pathogenic ★★ same condition
OAT c.199+2T>A Likely pathogenic ★★ same condition
OAT c.425-2A>G Pathogenic ★★ same condition
OAT c.520+1G>A Likely pathogenic ★★ same condition
OAT c.648+1G>A Likely pathogenic ★★ same condition
OAT c.772-1G>A Pathogenic/Likely pathogenic ★★ 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/oat-p-arg426ter (accessed [today's date]).

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