Is PTPRC p.Ser576Phe (c.1727C>T) pathogenic?

PTPRC p.Ser576Phe (c.1727C>T) is classified Uncertain significance in PTPRC (ClinVar, Single submitter, 1 submitter; last evaluated 2019-04-24). AlphaMissense: likely pathogenic (0.7929); Absent from gnomAD v4.1; Associated with immunodeficiency 104.

What condition is associated with PTPRC p.Ser576Phe (c.1727C>T)?

PTPRC p.Ser576Phe (c.1727C>T) is associated with immunodeficiency 104 (ClinVar).

How common is PTPRC p.Ser576Phe (c.1727C>T) in the general population?

PTPRC p.Ser576Phe (c.1727C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PTPRC p.Ser576Phe (c.1727C>T)?

AlphaMissense predicts likely pathogenic (score 0.7929) — an in-silico prediction, not a clinical call.

PTPRC p.Ser576Phe

c.1727C>T · rs1654236550 · VCV950764

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7929 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

immunodeficiency 104

Computational evidence

Protein change
AlphaMissense	0.7929	likely pathogenic
REVEL	0.19	benign-leaning
SaProt	LLR -5.13	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.02	GERP 0.82
Regional constraint	o/e 0.89	unconstrained · MANE · 103 kb · p 0.0009 · regional, not allelic
Overall
CADD	19.76	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PTPRC
Protein: p.Ser576Phe
Coding: c.1727C>T
MANE Select: NM_002838
dbSNP: rs1654236550
Type: single nucleotide variant
Location: chr1:198728346 (GRCh38)
Gene constraint: LOEUF 0.343 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.22 · 6 PDB
Residue 576: a UniProt-annotated variant site (in imd105); the fibronectin type-iii 2 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 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
PTPRC p.Ala60Thr 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-ser576phe (accessed [today's date]).

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