Is PTPRCAP p.Arg69Cys (c.205C>T) pathogenic?

PTPRCAP p.Arg69Cys (c.205C>T) is classified Uncertain significance in PTPRCAP (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-13). AlphaMissense: likely benign (0.3273); Very rare (popmax 0.0027%, afr).

How common is PTPRCAP p.Arg69Cys (c.205C>T) in the general population?

PTPRCAP p.Arg69Cys (c.205C>T) is very rare (popmax 0.0027%, afr) (gnomAD).

What do computational predictors say about PTPRCAP p.Arg69Cys (c.205C>T)?

AlphaMissense predicts likely benign (score 0.3273) — an in-silico prediction, not a clinical call.

PTPRCAP p.Arg69Cys

c.205C>T · rs762585213 · VCV2236754

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3273 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0027%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.3273	likely benign
REVEL	0.33	indeterminate
SaProt	LLR -10.24	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 1,883 bp · p 0.61 · regional, not allelic
Overall
CADD	31.0	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 0.0027% African / African-American · 2/74,196 alleles

Filtering AF 0.000447% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000167%

Overall 0.000382% 6/1,570,434 alleles · very rare exomes 6/1,418,072 · genomes 0/152,362 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0027%	37,098
Admixed American	0.00187%	53,394
Finnishnot grpmax-eligible	0.00168%	59,380
European (non-Finnish)	0.000173%	578,938

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.Arg69Cys
Coding: c.205C>T
MANE Select: NM_005608
dbSNP: rs762585213
Type: single nucleotide variant
Location: chr11:67436149 (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.Arg69His Uncertain significance ★ ⚠ same residue
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

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-arg69cys (accessed [today's date]).

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