Is PTPRC p.Ala703Ser (c.2107G>T) pathogenic?

PTPRC p.Ala703Ser (c.2107G>T) is classified Uncertain significance in PTPRC (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-20). AlphaMissense: likely benign (0.0821); Absent from gnomAD v4.1; Associated with immunodeficiency 104.

What condition is associated with PTPRC p.Ala703Ser (c.2107G>T)?

PTPRC p.Ala703Ser (c.2107G>T) is associated with immunodeficiency 104 (ClinVar).

How common is PTPRC p.Ala703Ser (c.2107G>T) in the general population?

PTPRC p.Ala703Ser (c.2107G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PTPRC p.Ala703Ser (c.2107G>T)?

AlphaMissense predicts likely benign (score 0.0821) — an in-silico prediction, not a clinical call.

PTPRC p.Ala703Ser

c.2107G>T · rs1654442187 · VCV958174

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0821 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

immunodeficiency 104

Computational evidence

Protein change
AlphaMissense	0.0821	likely benign
REVEL	0.309	indeterminate
SaProt	LLR -4.63	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.96	GERP 0.49
Regional constraint	o/e 0.89	unconstrained · MANE · 103 kb · p 0.0009 · regional, not allelic
Overall
CADD	17.22	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

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.Ala703Ser
Coding: c.2107G>T
MANE Select: NM_002838
dbSNP: rs1654442187
Type: single nucleotide variant
Location: chr1:198732521 (GRCh38)
Gene constraint: LOEUF 0.343 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.22 · 6 PDB
Residue 703: a turn; 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 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-ala703ser (accessed [today's date]).

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