Is MATK p.Ala327Ser (c.979G>T) pathogenic?

MATK p.Ala327Ser (c.979G>T) is classified Uncertain significance in MATK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-26). AlphaMissense: likely benign (0.0732); Ultra-rare (popmax 0.0107%, afr).

How common is MATK p.Ala327Ser (c.979G>T) in the general population?

MATK p.Ala327Ser (c.979G>T) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

What do computational predictors say about MATK p.Ala327Ser (c.979G>T)?

AlphaMissense predicts likely benign (score 0.0732) — an in-silico prediction, not a clinical call.

MATK p.Ala327Ser

c.979G>T · VCV3543626

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0732 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0732	likely benign
REVEL	0.118	moderately benign-leaning
SaProt	LLR -6.98	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 0.026	GERP -3.7
Regional constraint	o/e 0.82	unconstrained · MANE · 6,949 bp · p 2.3e-06 · regional, not allelic
Overall
CADD	3.899	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 0.0107% African / African-American · 8/74,938 alleles

Filtering AF 0.00528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.00062% 10/1,613,166 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0107%	9,367
European (non-Finnish)	0.000169%	590,005

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.Ala327Ser
Coding: c.979G>T
MANE Select: NM_139355
Type: single nucleotide variant
Location: chr19:3779400 (GRCh38)
Gene constraint: LOEUF 0.921 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.24 · 3 PDB
Residue 327: 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.Ala466Thr Uncertain significance ★ ⚠ same type
MATK p.Ala496Asp Uncertain significance ★ ⚠ same type
MATK p.Arg151Cys 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-ala327ser (accessed [today's date]).

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