Is OMD p.Phe72Leu (c.214T>C) pathogenic?

OMD p.Phe72Leu (c.214T>C) is classified Uncertain significance in OMD (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-06). AlphaMissense: likely pathogenic (0.7329); Ultra-rare (popmax 0.0112%, nfe).

How common is OMD p.Phe72Leu (c.214T>C) in the general population?

OMD p.Phe72Leu (c.214T>C) is ultra-rare (popmax 0.0112%, nfe) (gnomAD).

What do computational predictors say about OMD p.Phe72Leu (c.214T>C)?

AlphaMissense predicts likely pathogenic (score 0.7329) — an in-silico prediction, not a clinical call.

OMD p.Phe72Leu

c.214T>C · rs374973890 · VCV2265188

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7329 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0112%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7329	likely pathogenic
REVEL	0.124	moderately benign-leaning
SaProt	LLR -7.16	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 2,403 bp · p 0.054 · regional, not allelic
Overall
CADD	23.4	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 0.0112% European (non-Finnish) · 132/1,179,970 alleles

Filtering AF 0.00961% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00904%

Overall 0.00836% 135/1,613,932 alleles · ultra-rare exomes 132/1,461,770 · genomes 3/152,162 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0112%	8,939
Remaining individualsnot grpmax-eligible	0.0048%	20,827

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.Phe72Leu
Coding: c.214T>C
MANE Select: NM_005014
dbSNP: rs374973890
Type: single nucleotide variant
Location: chr9:92417345 (GRCh38)
Gene constraint: LOEUF 0.757 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 81.82 · 1 PDB
Residue 72: the lrrnt domain

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

Similar variants

OMD p.Arg336His Uncertain significance ★ same type
OMD p.Arg366Gln Uncertain significance ★ ⚠ same type
OMD p.Arg81Cys Uncertain significance ★ ⚠ same type
OMD p.Asn101Ser Uncertain significance ★ ⚠ same type
OMD p.Asn172Ser Uncertain significance ★ same type
OMD p.Asn187Asp Uncertain significance ★ ⚠ same type
OMD p.Asn369Thr Uncertain significance ★ ⚠ same type
OMD p.Asp30Asn Uncertain significance ★ ⚠ same type

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-phe72leu (accessed [today's date]).

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