Is PTPRF p.Arg407Ser (c.1219C>A) pathogenic?

PTPRF p.Arg407Ser (c.1219C>A) is classified Uncertain significance in PTPRF (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-28). AlphaMissense: ambiguous (0.4844); Very rare (popmax 0.00299%, nfe).

How common is PTPRF p.Arg407Ser (c.1219C>A) in the general population?

PTPRF p.Arg407Ser (c.1219C>A) is very rare (popmax 0.00299%, nfe) (gnomAD).

What do computational predictors say about PTPRF p.Arg407Ser (c.1219C>A)?

AlphaMissense predicts ambiguous (score 0.4844) — an in-silico prediction, not a clinical call.

PTPRF p.Arg407Ser

c.1219C>A · rs748429132 · VCV3149351

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4844 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00299%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4844	ambiguous
REVEL	0.196	benign-leaning
SaProt	LLR -10.12	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 6,728 bp · p 0.011 · regional, not allelic
Overall
CADD	26.4	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 0.00299% European (non-Finnish) · 35/1,171,788 alleles

Filtering AF 0.00217% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00192%

Overall 0.00232% 37/1,594,152 alleles · very rare exomes 32/1,441,896 · genomes 5/152,256 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00299%	33,480
Admixed American	0.00173%	57,900
African / African-American	0.00134%	74,544

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.Arg407Ser
Coding: c.1219C>A
MANE Select: NM_002840
dbSNP: rs748429132
Type: single nucleotide variant
Location: chr1:43591241 (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.Arg407His 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-arg407ser (accessed [today's date]).

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