Is MOK p.Phe146Ser (c.437T>C) pathogenic?

MOK p.Phe146Ser (c.437T>C) is classified Uncertain significance in MOK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-26). AlphaMissense: likely pathogenic (0.9804); Very rare (popmax 0.00801%, afr).

How common is MOK p.Phe146Ser (c.437T>C) in the general population?

MOK p.Phe146Ser (c.437T>C) is very rare (popmax 0.00801%, afr) (gnomAD).

What do computational predictors say about MOK p.Phe146Ser (c.437T>C)?

AlphaMissense predicts likely pathogenic (score 0.9804) — an in-silico prediction, not a clinical call.

MOK p.Phe146Ser

c.437T>C · rs1306942878 · VCV2220348

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9804 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9804	likely pathogenic · top 4% in MOK
REVEL	0.914	moderately pathogenic-leaning
SaProt	LLR -13.53	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.8	GERP 2.1, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 76 kb · p 0.69 · regional, not allelic
Overall
CADD	28.5	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 0.00801% African / African-American · 6/74,952 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00228%

Overall 0.00062% 10/1,613,966 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,492
Remaining individualsnot grpmax-eligible	0.0048%	20,828
South Asian	0.0011%	91,066

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.Phe146Ser
Coding: c.437T>C
MANE Select: NM_014226
dbSNP: rs1306942878
Type: single nucleotide variant
Location: chr14:102250965 (GRCh38)
Gene constraint: LOEUF 1.292 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.98
Residue 146: the protein kinase domain

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

Similar variants

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
MOK p.Arg168Trp 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-phe146ser (accessed [today's date]).

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