Is PTPRC p.Ile799Phe (c.2395A>T) pathogenic?

PTPRC p.Ile799Phe (c.2395A>T) is classified Uncertain significance in PTPRC (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-18). AlphaMissense: likely pathogenic (0.5878); Ultra-rare (popmax 0.0563%, eas); Associated with immunodeficiency 104.

What condition is associated with PTPRC p.Ile799Phe (c.2395A>T)?

PTPRC p.Ile799Phe (c.2395A>T) is associated with immunodeficiency 104 (ClinVar).

How common is PTPRC p.Ile799Phe (c.2395A>T) in the general population?

PTPRC p.Ile799Phe (c.2395A>T) is ultra-rare (popmax 0.0563%, eas) (gnomAD).

What do computational predictors say about PTPRC p.Ile799Phe (c.2395A>T)?

AlphaMissense predicts likely pathogenic (score 0.5878) — an in-silico prediction, not a clinical call.

PTPRC p.Ile799Phe

c.2395A>T · rs185420520 · VCV464442

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5878 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0563%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

immunodeficiency 104

Computational evidence

Protein change
AlphaMissense	0.5878	likely pathogenic
REVEL	0.562	indeterminate
SaProt	LLR -10.21	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.4	GERP -1.9, phastCons 0.001
Regional constraint	o/e 0.89	unconstrained · MANE · 103 kb · p 0.0009 · regional, not allelic
Overall
CADD	14.83	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0563% East Asian · 25/44,368 alleles

Filtering AF 0.0391% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0334%

Overall 0.00175% 28/1,599,444 alleles · ultra-rare exomes 24/1,447,538 · genomes 4/151,906 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0563%	1,775
Remaining individualsnot grpmax-eligible	0.00486%	20,573

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.Ile799Phe
Coding: c.2395A>T
MANE Select: NM_002838
dbSNP: rs185420520
Type: single nucleotide variant
Location: chr1:198735244 (GRCh38)
Gene constraint: LOEUF 0.343 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.22 · 6 PDB
Residue 799: a β-strand; a UniProt-annotated variant site (in imd105); the tyrosine-protein phosphatase 1 domain

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

Disease context

immunodeficiency 104 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PTPRC p.Ile799Thr Uncertain significance ★ ⚠ 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.Ala191Val 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-ile799phe (accessed [today's date]).

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