Is PTPRC p.Val779Ile (c.2335G>A) pathogenic?

PTPRC p.Val779Ile (c.2335G>A) is classified Uncertain significance in PTPRC (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-23). AlphaMissense: likely benign (0.0718); Ultra-rare (popmax 0.0152%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PTPRC p.Val779Ile (c.2335G>A)?

PTPRC p.Val779Ile (c.2335G>A) is associated with Inborn genetic diseases, immunodeficiency 104 (ClinVar).

How common is PTPRC p.Val779Ile (c.2335G>A) in the general population?

PTPRC p.Val779Ile (c.2335G>A) is ultra-rare (popmax 0.0152%, nfe) (gnomAD).

What do computational predictors say about PTPRC p.Val779Ile (c.2335G>A)?

AlphaMissense predicts likely benign (score 0.0718) — an in-silico prediction, not a clinical call.

PTPRC p.Val779Ile

c.2335G>A · rs146726593 · VCV1379599

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0718 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0152%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0718	likely benign
REVEL	0.119	moderately benign-leaning
SaProt	LLR -4.05	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 0.56	GERP -0.78, phastCons 0.041
Regional constraint	o/e 0.89	unconstrained · MANE · 103 kb · p 0.0009 · regional, not allelic
Overall
CADD	1.461	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 0.0152% European (non-Finnish) · 179/1,173,984 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0127%

Overall 0.0121% 194/1,604,244 alleles · ultra-rare exomes 183/1,452,556 · genomes 11/151,688 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0152%	6,559
Remaining individualsnot grpmax-eligible	0.0113%	8,853
Admixed American	0.00671%	14,899
African / African-American	0.00536%	18,658

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.Val779Ile
Coding: c.2335G>A
MANE Select: NM_002838
dbSNP: rs146726593
Type: single nucleotide variant
Location: chr1:198735184 (GRCh38)
Gene constraint: LOEUF 0.343 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.22 · 6 PDB
Residue 779: 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

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

Also linked: immunodeficiency 104

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.Ala1189Val 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-val779ile (accessed [today's date]).

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