Is MAST4 p.Pro1007Arg (c.3020C>G) pathogenic?

MAST4 p.Pro1007Arg (c.3020C>G) is classified Uncertain significance in MAST4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-02). AlphaMissense: likely benign (0.1226); Absent from gnomAD v4.1.

How common is MAST4 p.Pro1007Arg (c.3020C>G) in the general population?

MAST4 p.Pro1007Arg (c.3020C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAST4 p.Pro1007Arg (c.3020C>G)?

AlphaMissense predicts likely benign (score 0.1226) — an in-silico prediction, not a clinical call.

MAST4 p.Pro1007Arg

c.3020C>G · VCV3293433

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1226 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1226	likely benign
REVEL	0.133	moderately benign-leaning
SaProt	LLR -6.70	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 4	GERP 6.2, phastCons 0.98
Regional constraint	o/e 0.83	unconstrained · MANE · 21 kb · p 4.5e-06 · regional, not allelic
Overall
CADD	20.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MAST4
Protein: p.Pro1007Arg
Coding: c.3020C>G
MANE Select: NM_001164664
Type: single nucleotide variant
Location: chr5:67145305 (GRCh38)
Gene constraint: LOEUF 0.66 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 43.32 · 1 PDB
Residue 1007: the 'disordered' region

Full MAST4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAST4 p.Arg2128Ser Benign ★★ same type
MAST4 p.Gln161= Benign ★★ same type
MAST4 p.Leu681= Benign ★★ same type
MAST4 p.Thr2354= Benign ★★ same type
MAST4 c.3526-3T>C Uncertain significance ★ same type
MAST4 c.642+40063G>C Uncertain significance ★ same type
MAST4 c.642+40066T>C Uncertain significance ★ same type
MAST4 c.642+40075G>A 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/mast4-p-pro1007arg (accessed [today's date]).

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