Is PTPRC p.Ala191Val (c.572C>T) pathogenic?

PTPRC p.Ala191Val (c.572C>T) is classified Uncertain significance in PTPRC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-01). AlphaMissense: likely benign (0.0975); Very rare (popmax 0.00801%, afr); Associated with Inborn genetic diseases.

What condition is associated with PTPRC p.Ala191Val (c.572C>T)?

PTPRC p.Ala191Val (c.572C>T) is associated with Inborn genetic diseases, immunodeficiency 104 (ClinVar).

How common is PTPRC p.Ala191Val (c.572C>T) in the general population?

PTPRC p.Ala191Val (c.572C>T) is very rare (popmax 0.00801%, afr) (gnomAD).

What do computational predictors say about PTPRC p.Ala191Val (c.572C>T)?

AlphaMissense predicts likely benign (score 0.0975) — an in-silico prediction, not a clinical call.

PTPRC p.Ala191Val

c.572C>T · rs1276140091 · VCV1063375

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0975 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0975	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -6.69	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.20 · evaluated, not missing
Pangolin	Δ0.27	loss · gain 0.00 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 0.77	GERP -2.9
Regional constraint	o/e 0.89	unconstrained · MANE · 103 kb · p 0.0009 · regional, not allelic
Overall
CADD	3.444	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 0.00801% African / African-American · 6/74,908 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.00142% 23/1,614,056 alleles · very rare exomes 21/1,461,888 · genomes 2/152,168 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,485
East Asian	0.00668%	14,963
European (non-Finnish)	0.0011%	90,772
South Asian	0.0011%	91,090

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: PTPRC
Protein: p.Ala191Val
Coding: c.572C>T
MANE Select: NM_002838
dbSNP: rs1276140091
Type: single nucleotide variant
Location: chr1:198702519 (GRCh38)
Gene constraint: LOEUF 0.343 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.22 · 6 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: immunodeficiency 104

Similar variants

PTPRC p.Ala191= Likely benign ★ same residue
PTPRC c.583+1G>A Likely pathogenic ★★ same condition
PTPRC c.583+1G>T Likely pathogenic ★★ same condition
PTPRC p.Arg890Ter Pathogenic/Likely pathogenic ★★ same condition
PTPRC c.1830-3C>T Uncertain significance ★★ same condition
PTPRC c.3509+5G>A Uncertain significance ★★ same condition
PTPRC p.Ala113Ser Uncertain significance ★★ ⚠ same condition
PTPRC p.Ala1189Val Uncertain significance ★★ same condition

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/ptprc-p-ala191val (accessed [today's date]).

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