Is PTPRG p.Val95Phe (c.283G>T) pathogenic?

PTPRG p.Val95Phe (c.283G>T) is classified Uncertain significance in PTPRG (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-23). AlphaMissense: likely benign (0.1728); Ultra-rare (popmax 0.0354%, nfe).

How common is PTPRG p.Val95Phe (c.283G>T) in the general population?

PTPRG p.Val95Phe (c.283G>T) is ultra-rare (popmax 0.0354%, nfe) (gnomAD).

What do computational predictors say about PTPRG p.Val95Phe (c.283G>T)?

AlphaMissense predicts likely benign (score 0.1728) — an in-silico prediction, not a clinical call.

PTPRG p.Val95Phe

c.283G>T · rs141896316 · VCV2352126

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1728 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0354%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1728	likely benign
REVEL	0.382	indeterminate
SaProt	LLR -7.29	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 2.3, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 606 kb · p 0.1 · regional, not allelic
Overall
CADD	22.1	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 0.0354% European (non-Finnish) · 418/1,180,020 alleles

Filtering AF 0.0325% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0315%

Overall 0.0273% 441/1,614,168 alleles · ultra-rare exomes 419/1,461,860 · genomes 22/152,308 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0354%	2,823
African / African-American	0.0187%	5,359
Middle Eastern	0.0165%	6,060
Remaining individualsnot grpmax-eligible	0.0128%	7,813

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: PTPRG
Protein: p.Val95Phe
Coding: c.283G>T
MANE Select: NM_002841
dbSNP: rs141896316
Type: single nucleotide variant
Location: chr3:61989717 (GRCh38)
Gene constraint: LOEUF 0.714 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.76 · 20 PDB
Residue 95: the alpha-carbonic anhydrase domain

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

Similar variants

PTPRG p.Val95Asp Uncertain significance ★ ⚠ same residue
PTPRG p.Val95Ile Uncertain significance ★ ⚠ same residue
PTPRG p.Ala614Thr Uncertain significance ★★ ⚠ same type
PTPRG p.Ile1333Thr Uncertain significance ★★ ⚠ same type
PTPRG p.Asn429= Likely benign ★★ same type
PTPRG p.His412= Benign ★★ same type
PTPRG p.Leu14= Benign ★★ same type
PTPRG p.Pro58= Benign ★★ 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/ptprg-p-val95phe (accessed [today's date]).

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