Is MATK p.Val336Ala (c.1007T>C) pathogenic?

MATK p.Val336Ala (c.1007T>C) is classified Uncertain significance in MATK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-09). AlphaMissense: ambiguous (0.533); Very rare (popmax 0.0018%, nfe).

How common is MATK p.Val336Ala (c.1007T>C) in the general population?

MATK p.Val336Ala (c.1007T>C) is very rare (popmax 0.0018%, nfe) (gnomAD).

What do computational predictors say about MATK p.Val336Ala (c.1007T>C)?

AlphaMissense predicts ambiguous (score 0.533) — an in-silico prediction, not a clinical call.

MATK p.Val336Ala

c.1007T>C · VCV3543636

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.533 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0018%, nfe)

Computational evidence

Protein change
AlphaMissense	0.533	ambiguous
REVEL	0.461	indeterminate
SaProt	LLR -8.92	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 6,949 bp · p 2.3e-06 · regional, not allelic
Overall
CADD	26.9	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 0.0018% European (non-Finnish) · 21/1,166,094 alleles

Filtering AF 0.00116% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000982%

Overall 0.00145% 23/1,587,526 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0018%	55,528
Admixed American	0.00173%	57,688
Remaining individualsnot grpmax-eligible	0.00163%	61,274

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.Val336Ala
Coding: c.1007T>C
MANE Select: NM_139355
Type: single nucleotide variant
Location: chr19:3779182 (GRCh38)
Gene constraint: LOEUF 0.921 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.24 · 3 PDB
Residue 336: the protein kinase domain

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

Similar variants

MATK p.Val336Met 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-val336ala (accessed [today's date]).

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