Is PTPRR p.Val620Phe (c.1858G>T) pathogenic?

PTPRR p.Val620Phe (c.1858G>T) is classified Uncertain significance in PTPRR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-12). AlphaMissense: likely pathogenic (0.9011); No allele count reported in gnomAD v4.1 (AN 1,613,760).

How common is PTPRR p.Val620Phe (c.1858G>T) in the general population?

PTPRR p.Val620Phe (c.1858G>T) is no allele count reported in gnomAD v4.1 (AN 1,613,760) (gnomAD).

What do computational predictors say about PTPRR p.Val620Phe (c.1858G>T)?

AlphaMissense predicts likely pathogenic (score 0.9011) — an in-silico prediction, not a clinical call.

PTPRR p.Val620Phe

c.1858G>T · VCV4148074

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9011 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,760)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9011	likely pathogenic
REVEL	0.857	moderately pathogenic-leaning
SaProt	LLR -9.80	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.8	GERP 2.6, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 45 kb · p 0.006 · regional, not allelic
Overall
CADD	28.4	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

No allele count reported in gnomAD v4.1 (AN 1,613,760). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PTPRR
Protein: p.Val620Phe
Coding: c.1858G>T
MANE Select: NM_002849
Type: single nucleotide variant
Location: chr12:70656726 (GRCh38)
Gene constraint: LOEUF 0.633 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.59 · 1 PDB
Residue 620: the tyrosine-protein phosphatase domain; an α-helix

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

Similar variants

PTPRR p.Ala295Thr Uncertain significance ★ ⚠ same type
PTPRR p.Ala318Thr Uncertain significance ★ ⚠ same type
PTPRR p.Ala367Glu Uncertain significance ★ ⚠ same type
PTPRR p.Ala388Thr Uncertain significance ★ ⚠ same type
PTPRR p.Ala461Asp Uncertain significance ★ same type
PTPRR p.Ala577Gly Uncertain significance ★ ⚠ same type
PTPRR p.Ala616Val Uncertain significance ★ ⚠ same type
PTPRR p.Ala653Thr Uncertain significance ★ ⚠ same type

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/ptprr-p-val620phe (accessed [today's date]).

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