Is PTPRCAP p.Trp75Arg (c.223T>C) pathogenic?

PTPRCAP p.Trp75Arg (c.223T>C) is classified Uncertain significance in PTPRCAP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-26). AlphaMissense: likely pathogenic (0.7343); Very rare (popmax 8.58e-05%, nfe).

How common is PTPRCAP p.Trp75Arg (c.223T>C) in the general population?

PTPRCAP p.Trp75Arg (c.223T>C) is very rare (popmax 8.58e-05%, nfe) (gnomAD).

What do computational predictors say about PTPRCAP p.Trp75Arg (c.223T>C)?

AlphaMissense predicts likely pathogenic (score 0.7343) — an in-silico prediction, not a clinical call.

PTPRCAP p.Trp75Arg

c.223T>C · VCV4573949

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7343 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.58e-05%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7343	likely pathogenic
REVEL	0.285	benign-leaning
SaProt	LLR -7.64	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.8	GERP 1.7, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 1,883 bp · p 0.61 · regional, not allelic
Overall
CADD	25.0	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 8.58e-05% European (non-Finnish) · 1/1,165,752 alleles

Overall 6.31e-05% 1/1,585,556 alleles · very rare exomes 1/1,433,272 · genomes 0/152,284 · joint denominator

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: PTPRCAP
Protein: p.Trp75Arg
Coding: c.223T>C
MANE Select: NM_005608
Type: single nucleotide variant
Location: chr11:67436131 (GRCh38)

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

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/ptprcap-p-trp75arg (accessed [today's date]).

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