Is PTPRCAP p.Arg77His (c.230G>A) pathogenic?

PTPRCAP p.Arg77His (c.230G>A) is classified Uncertain significance in PTPRCAP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-01). AlphaMissense: likely benign (0.0841); Rare (popmax 0.1%, sas).

How common is PTPRCAP p.Arg77His (c.230G>A) in the general population?

PTPRCAP p.Arg77His (c.230G>A) is rare (popmax 0.1%, sas) (gnomAD).

What do computational predictors say about PTPRCAP p.Arg77His (c.230G>A)?

AlphaMissense predicts likely benign (score 0.0841) — an in-silico prediction, not a clinical call.

PTPRCAP p.Arg77His

c.230G>A · VCV4147708

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0841 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.1%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0841	likely benign
REVEL	0.009	strongly benign-leaning
SaProt	LLR -7.99	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.77	GERP -3.5, phastCons 0.001
Regional constraint	o/e 1.03	unconstrained · MANE · 1,883 bp · p 0.61 · regional, not allelic
Overall
CADD	15.78	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 0.1% South Asian · 89/88,808 alleles

Filtering AF 0.0833% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0771%

Overall 0.00741% 118/1,593,356 alleles · rare exomes 105/1,441,014 · genomes 13/152,342 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.1%	998
Middle Eastern	0.0166%	6,012
Remaining individualsnot grpmax-eligible	0.0114%	8,797
Admixed American	0.0035%	28,535
Finnishnot grpmax-eligible	0.00163%	61,324
European (non-Finnish)	0.00145%	68,813
African / African-American	0.00134%	74,708

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.Arg77His
Coding: c.230G>A
MANE Select: NM_005608
Type: single nucleotide variant
Location: chr11:67436124 (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-arg77his (accessed [today's date]).

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