Is PTPRQ p.Ala1069fs (c.3205del) pathogenic?

PTPRQ p.Ala1069fs (c.3205del) is classified Likely pathogenic in PTPRQ (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-03-14). Very rare (popmax 0.000263%, nfe); Associated with PTPRQ-related disorder.

What condition is associated with PTPRQ p.Ala1069fs (c.3205del)?

PTPRQ p.Ala1069fs (c.3205del) is associated with PTPRQ-related disorder (ClinVar).

How common is PTPRQ p.Ala1069fs (c.3205del) in the general population?

PTPRQ p.Ala1069fs (c.3205del) is very rare (popmax 0.000263%, nfe) (gnomAD).

PTPRQ p.Ala1069fs

c.3205del · rs1450763362 · VCV2633574

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000263%, nfe)

Conditions

PTPRQ-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 21 of 45
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.21	GERP -5.4, phastCons 0.67
Overall
CADD	27.9	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000263% European (non-Finnish) · 3/1,142,076 alleles

Filtering AF 7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000259% 4/1,541,544 alleles · very rare exomes 2/1,389,370 · genomes 2/152,174 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00168%	59,668
European (non-Finnish)grpmax	0.000263%	380,691

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: PTPRQ
Protein: p.Ala1069fs
Coding: c.3205del
MANE Select: NM_001145026
dbSNP: rs1450763362
Type: Deletion
Location: chr12:80541605 (GRCh38)
Gene constraint: LOEUF 0.941 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 75.35 · 1 PDB
Residue 1069: the fibronectin type-iii 11 domain

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

Disease context

PTPRQ-related disorder

Similar variants

PTPRQ p.Ala1398fs Likely pathogenic ★ same condition
PTPRQ p.Val1578fs Likely pathogenic ★ same condition
PTPRQ p.Asn579fs Likely pathogenic same condition
PTPRQ c.6025-1G>A Pathogenic/Likely pathogenic ★★ same condition
PTPRQ p.Gln1336Ter Pathogenic ★★ same condition
PTPRQ p.Ala1494Val Uncertain significance ★★ ⚠ same condition
PTPRQ c.4015+1G>A Pathogenic ★ same condition
PTPRQ p.Cys97fs Pathogenic ★ 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/ptprq-p-ala1069fs (accessed [today's date]).

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