Is PTPRCAP p.Ala73Val (c.218C>T) pathogenic?

PTPRCAP p.Ala73Val (c.218C>T) is classified Uncertain significance in PTPRCAP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-17). AlphaMissense: likely benign (0.1172); Ultra-rare (popmax 0.0217%, amr).

How common is PTPRCAP p.Ala73Val (c.218C>T) in the general population?

PTPRCAP p.Ala73Val (c.218C>T) is ultra-rare (popmax 0.0217%, amr) (gnomAD).

What do computational predictors say about PTPRCAP p.Ala73Val (c.218C>T)?

AlphaMissense predicts likely benign (score 0.1172) — an in-silico prediction, not a clinical call.

PTPRCAP p.Ala73Val

c.218C>T · VCV3785168

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1172 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0217%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1172	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -7.75	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 1.4	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	11.51	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 0.0217% Admixed American · 12/55,204 alleles

Filtering AF 0.0124% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00981%

Overall 0.00569% 90/1,582,706 alleles · ultra-rare exomes 84/1,430,368 · genomes 6/152,338 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0217%	4,600
Middle Eastern	0.0167%	5,996
European (non-Finnish)	0.00575%	17,378
South Asian	0.00456%	21,954
Remaining individualsnot grpmax-eligible	0.00327%	30,574
African / African-American	0.00268%	37,260
East Asian	0.0023%	43,524
Finnishnot grpmax-eligible	0.00166%	60,412

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.Ala73Val
Coding: c.218C>T
MANE Select: NM_005608
Type: single nucleotide variant
Location: chr11:67436136 (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.Arg55His Uncertain significance ★ ⚠ same type
PTPRCAP p.Arg56Cys 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-ala73val (accessed [today's date]).

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