Is PTPRF p.Ala157= (c.471C>T) pathogenic?

PTPRF p.Ala157= (c.471C>T) is classified Benign in PTPRF (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-21). Common (popmax 31.5%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with PTPRF-related disorder.

What condition is associated with PTPRF p.Ala157= (c.471C>T)?

PTPRF p.Ala157= (c.471C>T) is associated with PTPRF-related disorder (ClinVar).

PTPRF p.Ala157=

Q: How common is PTPRF p.Ala157= (c.471C>T) in the general population?

PTPRF p.Ala157= (c.471C>T) is common (popmax 31.5%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.471C>T · rs1065771 · VCV3059678

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 31.5%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

PTPRF-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4	GERP -4.5
Overall
CADD	1.133	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 31.5% European (non-Finnish) · 371,323/1,179,632 alleles

Filtering AF 31.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 31.4%

Overall 29.7% 479,415/1,613,450 alleles · common exomes 442,799/1,461,338 · genomes 36,616/152,112 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	34.5%	3
European (non-Finnish)grpmax	31.5%	3
East Asian	30.5%	3
Remaining individualsnot grpmax-eligible	28.8%	3
Ashkenazi Jewishnot grpmax-eligible	27.5%	4
South Asian	27%	4
Admixed American	25.5%	4
Amishnot grpmax-eligible	23%	4
Middle Eastern	20.9%	5
African / African-American	6.55%	15

Finnish 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.Ala157=
Coding: c.471C>T
MANE Select: NM_002840
dbSNP: rs1065771
Type: single nucleotide variant
Location: chr1:43569681 (GRCh38)
Gene constraint: LOEUF 0.348 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 82.43 · 13 PDB
Residue 157: a β-strand; the ig-like c2-type 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.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
PTPRF p.Ile1819= 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-ala157 (accessed [today's date]).

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