Is MST1 p.Pro605Ala (c.1813C>G) pathogenic?

MST1 p.Pro605Ala (c.1813C>G) is classified Uncertain significance in MST1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-19). Very rare (popmax 0.004%, afr).

How common is MST1 p.Pro605Ala (c.1813C>G) in the general population?

MST1 p.Pro605Ala (c.1813C>G) is very rare (popmax 0.004%, afr) (gnomAD).

MST1 p.Pro605Ala

c.1813C>G · VCV4553593

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.873	moderately pathogenic-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,922 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000496% 8/1,613,636 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0064%	15,616
African / African-Americangrpmax	0.004%	24,974
South Asian	0.0011%	91,084

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: MST1
Protein: p.Pro605Ala
Coding: c.1813C>G
MANE Select: NM_006282 · reported on NM_020998
Type: single nucleotide variant
Location: chr3:49684613 (GRCh38)
Structure: AlphaFold pLDDT 76.45 · 16 PDB

Full MST1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

STK4 p.Arg115Ter Pathogenic/Likely pathogenic ★★ same type
STK4 p.Arg117Ter Pathogenic ★★ same type
STK4 p.Arg148Ter Pathogenic ★★ same type
STK4 p.Arg245Ter Pathogenic/Likely pathogenic ★★ same type
STK4 p.Ala391Val Uncertain significance ★★ ⚠ same type
STK4 p.Ala479Ser Uncertain significance ★★ ⚠ same type
STK4 p.Arg310Gln Uncertain significance ★★ ⚠ same type
STK4 p.Arg310Pro 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/mst1-p-pro605ala (accessed [today's date]).

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