Is PPTC7 p.Gly28Ser (c.82G>A) pathogenic?

PPTC7 p.Gly28Ser (c.82G>A) is classified Uncertain significance in PPTC7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-27). AlphaMissense: likely benign (0.0902); Very rare (popmax 0.00271%, nfe).

How common is PPTC7 p.Gly28Ser (c.82G>A) in the general population?

PPTC7 p.Gly28Ser (c.82G>A) is very rare (popmax 0.00271%, nfe) (gnomAD).

What do computational predictors say about PPTC7 p.Gly28Ser (c.82G>A)?

AlphaMissense predicts likely benign (score 0.0902) — an in-silico prediction, not a clinical call.

PPTC7 p.Gly28Ser

c.82G>A · rs977371621 · VCV2210318

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0902 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00271%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0902	likely benign
REVEL	0.032	moderately benign-leaning
SaProt	LLR -7.57	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.7	GERP 1.3, phastCons 0.99
Regional constraint	o/e 0.54	unconstrained · MANE · 46 kb · p 1.6e-20 · regional, not allelic
Overall
CADD	20.3	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 0.00271% European (non-Finnish) · 31/1,142,324 alleles

Filtering AF 0.00194% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00169%

Overall 0.00208% 32/1,542,138 alleles · very rare exomes 27/1,390,478 · genomes 5/151,660 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00271%	36,849
South Asian	0.00119%	83,796

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: PPTC7
Protein: p.Gly28Ser
Coding: c.82G>A
MANE Select: NM_139283
dbSNP: rs977371621
Type: single nucleotide variant
Location: chr12:110582950 (GRCh38)
Gene constraint: LOEUF 0.421 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 88.84

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.Gly35Val 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-gly28ser (accessed [today's date]).

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