Is MOK p.Val45Phe (c.133G>T) pathogenic?

MOK p.Val45Phe (c.133G>T) is classified Uncertain significance in MOK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-04). AlphaMissense: likely pathogenic (0.87); Very rare (popmax 0.000339%, nfe).

How common is MOK p.Val45Phe (c.133G>T) in the general population?

MOK p.Val45Phe (c.133G>T) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about MOK p.Val45Phe (c.133G>T)?

AlphaMissense predicts likely pathogenic (score 0.87) — an in-silico prediction, not a clinical call.

MOK p.Val45Phe

c.133G>T · VCV3912404

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.87 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.87	likely pathogenic
REVEL	0.376	indeterminate
SaProt	LLR -15.00	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.3, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 76 kb · p 0.69 · regional, not allelic
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.000339% European (non-Finnish) · 4/1,179,474 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,613,354 alleles · very rare exomes 3/1,461,166 · genomes 1/152,188 · joint denominator

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: MOK
Protein: p.Val45Phe
Coding: c.133G>T
MANE Select: NM_014226
Type: single nucleotide variant
Location: chr14:102265902 (GRCh38)
Gene constraint: LOEUF 1.292 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.98
Residue 45: the protein kinase domain

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

Similar variants

MOK p.Val45Ala Uncertain significance ★ ⚠ same residue
MOK p.Lys137Asn Benign ★★ ⚠ same type
MOK p.Ala196Ser Uncertain significance ★ ⚠ same type
MOK p.Ala222Thr Uncertain significance ★ ⚠ same type
MOK p.Ala276Thr Uncertain significance ★ ⚠ same type
MOK p.Arg150Gln Uncertain significance ★ ⚠ same type
MOK p.Arg150Trp Uncertain significance ★ ⚠ same type
MOK p.Arg165Cys 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/mok-p-val45phe (accessed [today's date]).

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