Is OMD p.Leu96Phe (c.286C>T) pathogenic?

OMD p.Leu96Phe (c.286C>T) is classified Uncertain significance in OMD (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-16). AlphaMissense: likely pathogenic (0.5747); Very rare (popmax 0.00136%, nfe).

How common is OMD p.Leu96Phe (c.286C>T) in the general population?

OMD p.Leu96Phe (c.286C>T) is very rare (popmax 0.00136%, nfe) (gnomAD).

What do computational predictors say about OMD p.Leu96Phe (c.286C>T)?

AlphaMissense predicts likely pathogenic (score 0.5747) — an in-silico prediction, not a clinical call.

OMD p.Leu96Phe

c.286C>T · rs1381601912 · VCV2261881

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5747 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00136%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5747	likely pathogenic
REVEL	0.725	pathogenic-leaning
SaProt	LLR -7.23	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4.4	GERP 0.46, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 2,403 bp · p 0.054 · regional, not allelic
Overall
CADD	23.7	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 0.00136% European (non-Finnish) · 16/1,180,002 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00118% 19/1,613,978 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00312%	32,008
Remaining individualsnot grpmax-eligible	0.0016%	62,484
European (non-Finnish)grpmax	0.00136%	73,750

Finnish 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: OMD
Protein: p.Leu96Phe
Coding: c.286C>T
MANE Select: NM_001012267 · reported on NM_005014
dbSNP: rs1381601912
Type: single nucleotide variant
Location: chr9:92417273 (GRCh38)

Full OMD 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/omd-p-leu96phe (accessed [today's date]).

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