Is OAT p.Val105Ala (c.314T>C) pathogenic?

OAT p.Val105Ala (c.314T>C) is classified Conflicting classifications of pathogenicity in OAT (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2023-09-26). AlphaMissense: likely benign (0.0492); Rare (popmax 0.154%, eas); Associated with Inborn genetic diseases.

What condition is associated with OAT p.Val105Ala (c.314T>C)?

OAT p.Val105Ala (c.314T>C) is associated with Inborn genetic diseases, ornithine aminotransferase deficiency (ClinVar).

How common is OAT p.Val105Ala (c.314T>C) in the general population?

OAT p.Val105Ala (c.314T>C) is rare (popmax 0.154%, eas) (gnomAD).

What do computational predictors say about OAT p.Val105Ala (c.314T>C)?

AlphaMissense predicts likely benign (score 0.0492) — an in-silico prediction, not a clinical call.

OAT p.Val105Ala

c.314T>C · rs199957428 · VCV456521

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0492 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.154%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0492	likely benign
REVEL	0.283	benign-leaning
SaProt	LLR -2.42	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.42	GERP -3.8
Regional constraint	o/e 0.81	unconstrained · MANE · 14 kb · p 1.6e-05 · regional, not allelic
Overall
CADD	2.037	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

Grpmax group 0.154% East Asian · 69/44,856 alleles

Filtering AF 0.125% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.114%

Overall 0.00471% 76/1,613,194 alleles · rare exomes 67/1,460,854 · genomes 9/152,340 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.154%	650
Middle Eastern	0.056%	1,786
Remaining individualsnot grpmax-eligible	0.0032%	31,207
European (non-Finnish)	0.00017%	589,957

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.Val105Ala
Coding: c.314T>C
MANE Select: NM_000274
dbSNP: rs199957428
Type: single nucleotide variant
Location: chr10:124408851 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.29 · 35 PDB
Residue 105: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ornithine aminotransferase deficiency

Similar variants

OAT p.Val105Met Uncertain significance ★ ⚠ same residue
OAT p.Val105= 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-val105ala (accessed [today's date]).

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