Is MOK p.Pro200Ser (c.598C>T) pathogenic?

MOK p.Pro200Ser (c.598C>T) is classified Uncertain significance in MOK (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-30). AlphaMissense: likely pathogenic (0.8526); Very rare (popmax 8.48e-05%, nfe).

How common is MOK p.Pro200Ser (c.598C>T) in the general population?

MOK p.Pro200Ser (c.598C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about MOK p.Pro200Ser (c.598C>T)?

AlphaMissense predicts likely pathogenic (score 0.8526) — an in-silico prediction, not a clinical call.

MOK p.Pro200Ser

c.598C>T · rs2510034105 · VCV3195932

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8526 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8526	likely pathogenic
REVEL	0.598	indeterminate
SaProt	LLR -13.14	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 0.9, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 76 kb · p 0.69 · regional, not allelic
Overall
CADD	27.2	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 8.48e-05% European (non-Finnish) · 1/1,179,260 alleles

Overall 6.2e-05% 1/1,613,320 alleles · very rare exomes 1/1,460,998 · genomes 0/152,322 · 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.Pro200Ser
Coding: c.598C>T
MANE Select: NM_014226
dbSNP: rs2510034105
Type: single nucleotide variant
Location: chr14:102233782 (GRCh38)
Gene constraint: LOEUF 1.292 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.98
Residue 200: 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-pro200ser (accessed [today's date]).

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