Is OGN p.Ala78Val (c.233C>T) pathogenic?

OGN p.Ala78Val (c.233C>T) is classified Uncertain significance in OGN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-28). AlphaMissense: likely benign (0.0761); Ultra-rare (popmax 0.0236%, nfe).

How common is OGN p.Ala78Val (c.233C>T) in the general population?

OGN p.Ala78Val (c.233C>T) is ultra-rare (popmax 0.0236%, nfe) (gnomAD).

What do computational predictors say about OGN p.Ala78Val (c.233C>T)?

AlphaMissense predicts likely benign (score 0.0761) — an in-silico prediction, not a clinical call.

OGN p.Ala78Val

c.233C>T · rs146105137 · VCV3204159

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0761 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0236%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.0761	likely benign
REVEL	0.05	moderately benign-leaning
SaProt	LLR -5.28	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -2	GERP -4
Regional constraint	o/e 0.81	unconstrained · MANE · 18 kb · p 0.00036 · regional, not allelic
Overall
CADD	2.647	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 0.0236% European (non-Finnish) · 264/1,119,018 alleles

Filtering AF 0.0212% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0203%

Overall 0.0178% 275/1,544,858 alleles · ultra-rare exomes 258/1,392,798 · genomes 17/152,060 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.11%	912
European (non-Finnish)grpmax	0.0236%	4,239
Remaining individualsnot grpmax-eligible	0.0117%	8,583
Admixed American	0.00504%	19,847

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala78Val
Coding: c.233C>T
MANE Select: NM_014057
dbSNP: rs146105137
Type: single nucleotide variant
Location: chr9:92401127 (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-ala78val (accessed [today's date]).

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