Is MOBP p.Phe22Leu (c.66C>A) pathogenic?

MOBP p.Phe22Leu (c.66C>A) is classified Uncertain significance in MOBP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-23). AlphaMissense: likely pathogenic (0.9905); Very rare (popmax 0.00915%, nfe).

How common is MOBP p.Phe22Leu (c.66C>A) in the general population?

MOBP p.Phe22Leu (c.66C>A) is very rare (popmax 0.00915%, nfe) (gnomAD).

What do computational predictors say about MOBP p.Phe22Leu (c.66C>A)?

AlphaMissense predicts likely pathogenic (score 0.9905) — an in-silico prediction, not a clinical call.

MOBP p.Phe22Leu

c.66C>A · rs200848695 · VCV3187413

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9905 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00915%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9905	likely pathogenic · top 4% in MOBP
REVEL	0.359	indeterminate
SaProt	LLR -5.46	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 710 bp · p 4.9e-08 · regional, not allelic
Overall
CADD	24.6	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 0.00915% European (non-Finnish) · 108/1,180,050 alleles

Filtering AF 0.00774% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00719%

Overall 0.00712% 115/1,614,132 alleles · very rare exomes 111/1,461,892 · genomes 4/152,240 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00915%	10,926
Remaining individualsnot grpmax-eligible	0.008%	12,498
Admixed American	0.00167%	60,006
Finnishnot grpmax-eligible	0.00156%	64,046

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: MOBP
Protein: p.Phe22Leu
Coding: c.66C>A
MANE Select: NM_001393704
dbSNP: rs200848695
Type: single nucleotide variant
Location: chr3:39502135 (GRCh38)
Gene constraint: LOEUF 0.649 · pLI 0.81 (gnomAD)
Structure: AlphaFold pLDDT 55.69

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

Similar variants

MOBP c.206+5G>C Uncertain significance ★ same type
MOBP p.Ala64Thr Uncertain significance ★ same type
MOBP p.Ala6Thr Uncertain significance ★ ⚠ same type
MOBP p.Arg172Ser Uncertain significance ★ ⚠ same type
MOBP p.Gly9Cys Uncertain significance ★ ⚠ same type
MOBP p.Phe30Leu Uncertain significance ★ ⚠ same type
MOBP p.Pro76Arg Uncertain significance ★ same type
MOBP p.Pro84Ser 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/mobp-p-phe22leu (accessed [today's date]).

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