Is PPTC7 p.Tyr86Cys (c.257A>G) pathogenic?

PPTC7 p.Tyr86Cys (c.257A>G) is classified Uncertain significance in PPTC7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-14). AlphaMissense: likely pathogenic (0.6489); Absent from gnomAD v4.1.

How common is PPTC7 p.Tyr86Cys (c.257A>G) in the general population?

PPTC7 p.Tyr86Cys (c.257A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PPTC7 p.Tyr86Cys (c.257A>G)?

AlphaMissense predicts likely pathogenic (score 0.6489) — an in-silico prediction, not a clinical call.

PPTC7 p.Tyr86Cys

c.257A>G · VCV4571499

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6489 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.6489	likely pathogenic
REVEL	0.463	indeterminate
SaProt	LLR -9.03	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.8, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 46 kb · p 1.6e-20 · regional, not allelic
Overall
CADD	27.9	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

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: PPTC7
Protein: p.Tyr86Cys
Coding: c.257A>G
MANE Select: NM_139283
Type: single nucleotide variant
Location: chr12:110551935 (GRCh38)
Gene constraint: LOEUF 0.421 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 88.84
Residue 86: the ppm-type phosphatase domain

Full PPTC7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PPTC7 p.Asp158Asn Likely pathogenic ★ same type
PPTC7 p.Ala154Val Uncertain significance ★ ⚠ same type
PPTC7 p.Ala204Val Uncertain significance ★ ⚠ same type
PPTC7 p.Ala300Thr Uncertain significance ★ ⚠ same type
PPTC7 p.Asn280Ser Uncertain significance ★ ⚠ same type
PPTC7 p.Gly157Arg Uncertain significance ★ ⚠ same type
PPTC7 p.Gly167Asp Uncertain significance ★ ⚠ same type
PPTC7 p.Gly28Ser 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/pptc7-p-tyr86cys (accessed [today's date]).

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