Is OGN p.Asp89Val (c.266A>T) pathogenic?

OGN p.Asp89Val (c.266A>T) is classified Uncertain significance in OGN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-30). AlphaMissense: likely benign (0.094); Very rare (popmax 0.000102%, nfe).

How common is OGN p.Asp89Val (c.266A>T) in the general population?

OGN p.Asp89Val (c.266A>T) is very rare (popmax 0.000102%, nfe) (gnomAD).

What do computational predictors say about OGN p.Asp89Val (c.266A>T)?

AlphaMissense predicts likely benign (score 0.094) — an in-silico prediction, not a clinical call.

OGN p.Asp89Val

c.266A>T · VCV3409903

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.094 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000102%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.094	likely benign
REVEL	0.301	indeterminate
SaProt	LLR -6.13	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4.8	GERP 2.1, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 18 kb · p 0.00036 · regional, not allelic
Overall
CADD	21.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.000102% European (non-Finnish) · 1/981,134 alleles

Overall 0.000657% 1/152,252 alleles · very rare

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: OGN
Protein: p.Asp89Val
Coding: c.266A>T
MANE Select: NM_001012267 · reported on NM_014057
Type: single nucleotide variant
Location: chr9:92401094 (GRCh38)

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

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/ogn-p-asp89val (accessed [today's date]).

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