Is PTPRF p.Pro220Ser (c.658C>T) pathogenic?

PTPRF p.Pro220Ser (c.658C>T) is classified Uncertain significance in PTPRF (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-31). AlphaMissense: likely pathogenic (0.6481); Absent from gnomAD v4.1.

How common is PTPRF p.Pro220Ser (c.658C>T) in the general population?

PTPRF p.Pro220Ser (c.658C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PTPRF p.Pro220Ser (c.658C>T)?

AlphaMissense predicts likely pathogenic (score 0.6481) — an in-silico prediction, not a clinical call.

PTPRF p.Pro220Ser

c.658C>T · rs2546695938 · VCV2274821

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6481 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6481	likely pathogenic
REVEL	0.247	benign-leaning
SaProt	LLR -10.50	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 46 kb · p 1.7e-13 · regional, not allelic
Overall
CADD	27.8	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

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: PTPRF
Protein: p.Pro220Ser
Coding: c.658C>T
MANE Select: NM_002840
dbSNP: rs2546695938
Type: single nucleotide variant
Location: chr1:43578899 (GRCh38)
Gene constraint: LOEUF 0.348 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 82.43 · 13 PDB
Residue 220: the ig-like c2-type 2 domain; an α-helix

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

Similar variants

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
PTPRF p.Ala356Ser Likely 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-pro220ser (accessed [today's date]).

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