Is PTPRF p.Ser31Arg (c.93C>G) pathogenic?

PTPRF p.Ser31Arg (c.93C>G) is classified Uncertain significance in PTPRF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-13). AlphaMissense: likely pathogenic (0.5805); Very rare (popmax 0.00891%, eas).

How common is PTPRF p.Ser31Arg (c.93C>G) in the general population?

PTPRF p.Ser31Arg (c.93C>G) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about PTPRF p.Ser31Arg (c.93C>G)?

AlphaMissense predicts likely pathogenic (score 0.5805) — an in-silico prediction, not a clinical call.

PTPRF p.Ser31Arg

c.93C>G · rs763748777 · VCV2464185

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5805 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5805	likely pathogenic
REVEL	0.156	moderately benign-leaning
SaProt	LLR -6.25	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.1	GERP 1.8, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 46 kb · p 1.7e-13 · regional, not allelic
Overall
CADD	23.0	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 0.00891% East Asian · 4/44,888 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000744% 12/1,613,622 alleles · very rare exomes 11/1,461,420 · genomes 1/152,202 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,222
South Asian	0.0033%	30,347
Remaining individualsnot grpmax-eligible	0.0032%	31,232
European (non-Finnish)	0.000254%	393,239

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.Ser31Arg
Coding: c.93C>G
MANE Select: NM_002840
dbSNP: rs763748777
Type: single nucleotide variant
Location: chr1:43553493 (GRCh38)
Gene constraint: LOEUF 0.348 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 82.43 · 13 PDB
Residue 31: a β-strand

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-ser31arg (accessed [today's date]).

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