Is MST1R p.Arg455= (c.1365C>A) pathogenic?

MST1R p.Arg455= (c.1365C>A) is classified Likely benign in MST1R (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-09). Ultra-rare (popmax 0.0175%, nfe); Associated with MST1R-related disorder.

What condition is associated with MST1R p.Arg455= (c.1365C>A)?

MST1R p.Arg455= (c.1365C>A) is associated with MST1R-related disorder (ClinVar).

How common is MST1R p.Arg455= (c.1365C>A) in the general population?

MST1R p.Arg455= (c.1365C>A) is ultra-rare (popmax 0.0175%, nfe) (gnomAD).

MST1R p.Arg455=

c.1365C>A · rs143816851 · VCV3035390

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0175%, nfe)

Conditions

MST1R-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.39	GERP -3.7, phastCons 0.17
Overall
CADD	6.114	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0175% European (non-Finnish) · 206/1,180,048 alleles

Filtering AF 0.0155% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0147%

Overall 0.0136% 219/1,614,038 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0176%	5,681
European (non-Finnish)grpmax	0.0175%	5,728
African / African-American	0.00267%	37,464

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: MST1R
Protein: p.Arg455=
Coding: c.1365C>A
MANE Select: NM_002447
dbSNP: rs143816851
Type: single nucleotide variant
Location: chr3:49899129 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.23 · 4 PDB
Residue 455: a β-strand; the sema domain

Full MST1R gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

MST1R-related disorder

Similar variants

MST1R c.3811-10C>A Benign same condition
MST1R p.Arg1335Gly Benign same condition
MST1R p.Arg322Gln Benign same condition
MST1R p.Arg910= Benign same condition
MST1R p.Asn778Thr Likely benign same condition
MST1R p.Asp805= Likely benign same condition
MST1R p.Gly851= Likely benign same condition
MST1R p.Ile786= Likely benign same condition

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/mst1r-p-arg455 (accessed [today's date]).

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