Is MOK p.Ala196Ser (c.586G>T) pathogenic?

MOK p.Ala196Ser (c.586G>T) is classified Uncertain significance in MOK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-23). AlphaMissense: likely benign (0.0963); Very rare (popmax 8.48e-05%, nfe).

How common is MOK p.Ala196Ser (c.586G>T) in the general population?

MOK p.Ala196Ser (c.586G>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about MOK p.Ala196Ser (c.586G>T)?

AlphaMissense predicts likely benign (score 0.0963) — an in-silico prediction, not a clinical call.

MOK p.Ala196Ser

c.586G>T · rs757188060 · VCV3195902

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0963 · ACMG-weighted

gnomAD v4.1

Rare

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

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0963	likely benign
REVEL	0.104	moderately benign-leaning
SaProt	LLR -5.74	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.67	GERP -1.7, phastCons 0.2
Regional constraint	o/e 0.98	unconstrained · MANE · 76 kb · p 0.69 · regional, not allelic
Overall
CADD	11.36	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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) · 1/1,179,182 alleles

Overall 6.2e-05% 1/1,612,688 alleles · very rare exomes 1/1,460,444 · genomes 0/152,244 · 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.Ala196Ser
Coding: c.586G>T
MANE Select: NM_014226
dbSNP: rs757188060
Type: single nucleotide variant
Location: chr14:102250816 (GRCh38)
Gene constraint: LOEUF 1.292 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.98
Residue 196: 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.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
MOK p.Arg294Trp 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-ala196ser (accessed [today's date]).

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