Is PTPRS p.Pro771Ser (c.2311C>T) pathogenic?

PTPRS p.Pro771Ser (c.2311C>T) is classified Uncertain significance in PTPRS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-18). AlphaMissense: likely benign (0.0823); Very rare (popmax 0.00445%, afr).

How common is PTPRS p.Pro771Ser (c.2311C>T) in the general population?

PTPRS p.Pro771Ser (c.2311C>T) is very rare (popmax 0.00445%, afr) (gnomAD).

What do computational predictors say about PTPRS p.Pro771Ser (c.2311C>T)?

AlphaMissense predicts likely benign (score 0.0823) — an in-silico prediction, not a clinical call.

PTPRS p.Pro771Ser

c.2311C>T · VCV3428253

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0823 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00445%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0823	likely benign
REVEL	0.058	moderately benign-leaning
SaProt	LLR -5.82	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 0.76, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 17 kb · p 0.00034 · regional, not allelic
Overall
CADD	23.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00445% African / African-American · 3/67,430 alleles

Filtering AF 0.00118% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000627%

Overall 0.00041% 6/1,465,118 alleles · very rare exomes 3/1,313,270 · genomes 3/151,848 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00445%	22,477
Remaining individualsnot grpmax-eligible	0.00179%	55,900
South Asian	0.00134%	74,760
European (non-Finnish)	9e-05%	1,110,756

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: PTPRS
Protein: p.Pro771Ser
Coding: c.2311C>T
MANE Select: NM_002850
Type: single nucleotide variant
Location: chr19:5229529 (GRCh38)
Gene constraint: LOEUF 0.378 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.94 · 6 PDB
Residue 771: the fibronectin type-iii 5 domain

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

Similar variants

PTPRS p.Arg1572Trp Uncertain significance ★★ ⚠ same type
PTPRS p.Ala87= Benign ★★ same type
PTPRS p.Ala972= Benign ★★ same type
PTPRS p.Asn1737= Benign ★★ same type
PTPRS p.Glu165= Likely benign ★★ same type
PTPRS p.Gly1107= Likely benign ★★ same type
PTPRS p.His1642= Benign ★★ same type
PTPRS p.Ile1741= 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/ptprs-p-pro771ser (accessed [today's date]).

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