Is PTPRF p.Arg407His (c.1220G>A) pathogenic?

PTPRF p.Arg407His (c.1220G>A) is classified Uncertain significance in PTPRF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-31). AlphaMissense: likely benign (0.0971); Very rare (popmax 0.00537%, afr).

How common is PTPRF p.Arg407His (c.1220G>A) in the general population?

PTPRF p.Arg407His (c.1220G>A) is very rare (popmax 0.00537%, afr) (gnomAD).

What do computational predictors say about PTPRF p.Arg407His (c.1220G>A)?

AlphaMissense predicts likely benign (score 0.0971) — an in-silico prediction, not a clinical call.

PTPRF p.Arg407His

c.1220G>A · rs373662568 · VCV2352031

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0971 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00537%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0971	likely benign
REVEL	0.317	indeterminate
SaProt	LLR -9.03	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.1, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 6,728 bp · p 0.011 · regional, not allelic
Overall
CADD	29.3	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 0.00537% African / African-American · 4/74,516 alleles

Filtering AF 0.00301% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00269%

Overall 0.00358% 57/1,593,110 alleles · very rare exomes 49/1,440,860 · genomes 8/152,250 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00537%	18,629
Admixed American	0.00519%	19,251
European (non-Finnish)	0.00393%	25,463
Remaining individualsnot grpmax-eligible	0.00324%	30,831
South Asian	0.00223%	44,835

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: PTPRF
Protein: p.Arg407His
Coding: c.1220G>A
MANE Select: NM_002840
dbSNP: rs373662568
Type: single nucleotide variant
Location: chr1:43591242 (GRCh38)
Gene constraint: LOEUF 0.348 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 82.43 · 13 PDB
Residue 407: the 'disordered' region; a β-strand; the fibronectin type-iii 1 domain

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

Similar variants

PTPRF p.Arg407Ser Uncertain significance ★ ⚠ same residue
PTPRF p.Gly1143Ser Uncertain significance ★★ ⚠ same type
PTPRF p.His1730Gln Uncertain significance ★★ ⚠ same type
PTPRF c.1531+9G>A Benign/Likely benign ★★ same type
PTPRF c.1668+10G>C Benign/Likely benign ★★ same type
PTPRF c.237+5G>A Benign ★★ same type
PTPRF c.3974-9C>T Benign ★★ same type
PTPRF p.Ala1659= Benign ★★ 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/ptprf-p-arg407his (accessed [today's date]).

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