Is PTPRCAP p.Arg56Cys (c.166C>T) pathogenic?

PTPRCAP p.Arg56Cys (c.166C>T) is classified Uncertain significance in PTPRCAP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-22). AlphaMissense: likely benign (0.2531); Very rare (popmax 0.00278%, nfe).

How common is PTPRCAP p.Arg56Cys (c.166C>T) in the general population?

PTPRCAP p.Arg56Cys (c.166C>T) is very rare (popmax 0.00278%, nfe) (gnomAD).

What do computational predictors say about PTPRCAP p.Arg56Cys (c.166C>T)?

AlphaMissense predicts likely benign (score 0.2531) — an in-silico prediction, not a clinical call.

PTPRCAP p.Arg56Cys

c.166C>T · VCV3785169

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2531 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00278%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2531	likely benign
REVEL	0.216	benign-leaning
SaProt	LLR -8.64	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 12	GERP 1.7, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 1,883 bp · p 0.61 · regional, not allelic
Overall
CADD	32.0	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 0.00278% European (non-Finnish) · 32/1,150,894 alleles

Filtering AF 0.00201% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00172%

Overall 0.00232% 36/1,554,290 alleles · very rare exomes 35/1,402,078 · genomes 1/152,212 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00278%	35,965
East Asian	0.00241%	41,512
South Asian	0.00235%	42,538
Remaining individualsnot grpmax-eligible	0.00166%	60,298

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.Arg56Cys
Coding: c.166C>T
MANE Select: NM_005608
Type: single nucleotide variant
Location: chr11:67436188 (GRCh38)
Gene constraint: LOEUF 1.487 · pLI 0.50 (gnomAD)
Structure: AlphaFold pLDDT 58.14

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

Similar variants

PTPRCAP p.Ala137Val Uncertain significance ★ ⚠ same type
PTPRCAP p.Ala14Val Uncertain significance ★ ⚠ same type
PTPRCAP p.Ala169Val Uncertain significance ★ ⚠ same type
PTPRCAP p.Ala182Ser Uncertain significance ★ ⚠ same type
PTPRCAP p.Ala193Thr Uncertain significance ★ ⚠ same type
PTPRCAP p.Ala73Val Uncertain significance ★ ⚠ same type
PTPRCAP p.Arg55His Uncertain significance ★ ⚠ same type
PTPRCAP p.Arg59Cys Uncertain significance ★ ⚠ 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/ptprcap-p-arg56cys (accessed [today's date]).

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