Is PTPRF p.Ser1654= (c.4962C>G) pathogenic?

PTPRF p.Ser1654= (c.4962C>G) is classified Likely benign in PTPRF (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-24). Very rare (popmax 0.00449%, nfe); Associated with PTPRF-related disorder.

What condition is associated with PTPRF p.Ser1654= (c.4962C>G)?

PTPRF p.Ser1654= (c.4962C>G) is associated with PTPRF-related disorder (ClinVar).

How common is PTPRF p.Ser1654= (c.4962C>G) in the general population?

PTPRF p.Ser1654= (c.4962C>G) is very rare (popmax 0.00449%, nfe) (gnomAD).

PTPRF p.Ser1654=

c.4962C>G · rs138934219 · VCV3043516

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00449%, nfe)

Conditions

PTPRF-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.054	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.42	GERP -4.5, phastCons 0.069
Overall
CADD	2.988	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00449% European (non-Finnish) · 53/1,180,030 alleles

Filtering AF 0.0035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00318%

Overall 0.00359% 58/1,614,100 alleles · very rare exomes 54/1,461,856 · genomes 4/152,244 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0064%	15,623
European (non-Finnish)grpmax	0.00449%	22,265
South Asian	0.0011%	91,094

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: PTPRF
Protein: p.Ser1654=
Coding: c.4962C>G
MANE Select: NM_002840
dbSNP: rs138934219
Type: single nucleotide variant
Location: chr1:43619709 (GRCh38)
Gene constraint: LOEUF 0.348 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 82.43 · 13 PDB
Residue 1654: the tyrosine-protein phosphatase 2 domain

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

Disease context

PTPRF-related disorder

Similar variants

PTPRF c.3389+4T>G Likely benign same condition
PTPRF c.3974-829C>T Likely benign same condition
PTPRF c.4372-7C>T Likely benign same condition
PTPRF p.Ala157= Benign same condition
PTPRF p.Arg1286= Likely benign same condition
PTPRF p.Asn441= Likely benign same condition
PTPRF p.Asp562Asn Benign same condition
PTPRF p.Asp650= 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/ptprf-p-ser1654 (accessed [today's date]).

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