Is MATK p.Arg290Cys (c.868C>T) pathogenic?

MATK p.Arg290Cys (c.868C>T) is classified Uncertain significance in MATK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-10). AlphaMissense: likely benign (0.1353); Very rare (popmax 0.00669%, eas).

How common is MATK p.Arg290Cys (c.868C>T) in the general population?

MATK p.Arg290Cys (c.868C>T) is very rare (popmax 0.00669%, eas) (gnomAD).

What do computational predictors say about MATK p.Arg290Cys (c.868C>T)?

AlphaMissense predicts likely benign (score 0.1353) — an in-silico prediction, not a clinical call.

MATK p.Arg290Cys

c.868C>T · VCV4104453

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1353 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1353	likely benign
REVEL	0.243	benign-leaning
SaProt	LLR -10.32	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.53 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 6,949 bp · p 2.3e-06 · regional, not allelic
Overall
CADD	24.3	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 0.00669% East Asian · 3/44,818 alleles

Filtering AF 0.00178% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000892%

Overall 0.000993% 16/1,611,834 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,939
Finnishnot grpmax-eligible	0.00318%	31,434
European (non-Finnish)	0.000933%	107,221

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: MATK
Protein: p.Arg290Cys
Coding: c.868C>T
MANE Select: NM_139355
Type: single nucleotide variant
Location: chr19:3779592 (GRCh38)
Gene constraint: LOEUF 0.921 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.24 · 3 PDB
Residue 290: the protein kinase domain

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

Similar variants

MATK p.His34= Likely benign ★★ same type
MATK p.Pro465= Benign ★★ same type
MATK p.Ala113Ser Uncertain significance ★ ⚠ same type
MATK p.Ala132Ser Uncertain significance ★ ⚠ same type
MATK p.Ala150Thr Uncertain significance ★ ⚠ same type
MATK p.Ala327Ser Uncertain significance ★ ⚠ same type
MATK p.Ala466Thr Uncertain significance ★ ⚠ same type
MATK p.Ala496Asp 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/matk-p-arg290cys (accessed [today's date]).

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