Is OAT p.Phe172Ser (c.515T>C) pathogenic?

OAT p.Phe172Ser (c.515T>C) is classified Uncertain significance in OAT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-07-19). AlphaMissense: likely pathogenic (0.9208); Very rare (popmax 0.00611%, nfe); Associated with ornithine aminotransferase deficiency.

What condition is associated with OAT p.Phe172Ser (c.515T>C)?

OAT p.Phe172Ser (c.515T>C) is associated with ornithine aminotransferase deficiency (ClinVar).

How common is OAT p.Phe172Ser (c.515T>C) in the general population?

OAT p.Phe172Ser (c.515T>C) is very rare (popmax 0.00611%, nfe) (gnomAD).

How is Gyrate atrophy of choroid and retina inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about OAT p.Phe172Ser (c.515T>C)?

AlphaMissense predicts likely pathogenic (score 0.9208) — an in-silico prediction, not a clinical call.

OAT p.Phe172Ser

c.515T>C · rs746023526 · VCV2196663

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9208 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00611%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ornithine aminotransferase deficiency

Computational evidence

Protein change
AlphaMissense	0.9208	likely pathogenic
REVEL	0.76	pathogenic-leaning
SaProt	LLR -14.72	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, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 14 kb · p 1.6e-05 · regional, not allelic
Overall
CADD	29.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00611% European (non-Finnish) · 72/1,178,538 alleles

Filtering AF 0.00495% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00455%

Overall 0.0046% 74/1,610,226 alleles · very rare exomes 71/1,458,438 · genomes 3/151,788 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00611%	16,369
Remaining individualsnot grpmax-eligible	0.00321%	31,129

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.Phe172Ser
Coding: c.515T>C
MANE Select: NM_000274
dbSNP: rs746023526
Type: single nucleotide variant
Location: chr10:124408547 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.29 · 35 PDB
Residue 172: a β-strand

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

Disease context

ornithine aminotransferase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Gyrate atrophy of choroid and retina (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood
Prevalence: 1-9 / 100 000 (Finland)

Similar variants

OAT p.Phe172= Likely benign ★ same residue
OAT p.Phe172fs Pathogenic/Likely pathogenic ★★ 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-phe172ser (accessed [today's date]).

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