Is MATK p.Arg472Cys (c.1414C>T) pathogenic?

MATK p.Arg472Cys (c.1414C>T) is classified Uncertain significance in MATK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-30). AlphaMissense: likely benign (0.1672); Ultra-rare (popmax 0.0169%, mid).

How common is MATK p.Arg472Cys (c.1414C>T) in the general population?

MATK p.Arg472Cys (c.1414C>T) is ultra-rare (popmax 0.0169%, mid) (gnomAD).

What do computational predictors say about MATK p.Arg472Cys (c.1414C>T)?

AlphaMissense predicts likely benign (score 0.1672) — an in-silico prediction, not a clinical call.

MATK p.Arg472Cys

c.1414C>T · VCV3543628

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1672 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0169%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1672	likely benign
REVEL	0.415	indeterminate
SaProt	LLR -8.76	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7	GERP -0.66, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 6,949 bp · p 2.3e-06 · regional, not allelic
Overall
CADD	33.0	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 0.0169% Middle Eastern · 1/5,908 alleles

Filtering AF 0.00311% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00278%

Overall 0.00343% 54/1,575,758 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0169%	5,908
Remaining individualsnot grpmax-eligible	0.00493%	20,265
European (non-Finnish)	0.00403%	24,809
African / African-American	0.00275%	36,381
South Asian	0.00115%	86,644

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.Arg472Cys
Coding: c.1414C>T
MANE Select: NM_139355
Type: single nucleotide variant
Location: chr19:3778293 (GRCh38)
Gene constraint: LOEUF 0.921 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.24 · 3 PDB
Residue 472: the protein kinase domain

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

Similar variants

MATK p.Arg472His Uncertain significance ★ ⚠ same residue
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

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-arg472cys (accessed [today's date]).

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