Is MATK p.Arg151Cys (c.451C>T) pathogenic?

MATK p.Arg151Cys (c.451C>T) is classified Uncertain significance in MATK (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-22). AlphaMissense: likely pathogenic (0.7378); Very rare (popmax 0.00223%, eas).

How common is MATK p.Arg151Cys (c.451C>T) in the general population?

MATK p.Arg151Cys (c.451C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about MATK p.Arg151Cys (c.451C>T)?

AlphaMissense predicts likely pathogenic (score 0.7378) — an in-silico prediction, not a clinical call.

MATK p.Arg151Cys

c.451C>T · rs759655854 · VCV3123944

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7378 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7378	likely pathogenic
REVEL	0.416	indeterminate
SaProt	LLR -9.35	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -3.9, phastCons 0.6
Regional constraint	o/e 0.82	unconstrained · MANE · 6,949 bp · p 2.3e-06 · regional, not allelic
Overall
CADD	24.5	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 0.00223% East Asian · 1/44,874 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000434% 7/1,612,528 alleles · very rare exomes 7/1,460,238 · genomes 0/152,290 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,874
South Asian	0.0011%	91,044
European (non-Finnish)	0.000424%	235,947

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.Arg151Cys
Coding: c.451C>T
MANE Select: NM_139355
dbSNP: rs759655854
Type: single nucleotide variant
Location: chr19:3783945 (GRCh38)
Gene constraint: LOEUF 0.921 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.24 · 3 PDB
Residue 151: the sh2 domain; a β-strand

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-arg151cys (accessed [today's date]).

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