Is MATK p.Leu117Phe (c.349C>T) pathogenic?

MATK p.Leu117Phe (c.349C>T) is classified Uncertain significance in MATK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-25). AlphaMissense: ambiguous (0.5316); Very rare (popmax 8.48e-05%, nfe).

How common is MATK p.Leu117Phe (c.349C>T) in the general population?

MATK p.Leu117Phe (c.349C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about MATK p.Leu117Phe (c.349C>T)?

AlphaMissense predicts ambiguous (score 0.5316) — an in-silico prediction, not a clinical call.

MATK p.Leu117Phe

c.349C>T · VCV4052061

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5316 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5316	ambiguous
REVEL	0.264	benign-leaning
SaProt	LLR -8.00	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ1.00 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	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	29.1	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 8.48e-05% European (non-Finnish) · 1/1,178,586 alleles

Overall 6.85e-05% 1/1,459,114 alleles · very rare

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.Leu117Phe
Coding: c.349C>T
MANE Select: NM_139355
Type: single nucleotide variant
Location: chr19:3784137 (GRCh38)
Gene constraint: LOEUF 0.921 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.24 · 3 PDB

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-leu117phe (accessed [today's date]).

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