Is PPTC7 p.Gly35Val (c.104G>T) pathogenic?

PPTC7 p.Gly35Val (c.104G>T) is classified Uncertain significance in PPTC7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-25). AlphaMissense: likely benign (0.1653); No allele count reported in gnomAD v4.1 (AN 1,547,862).

How common is PPTC7 p.Gly35Val (c.104G>T) in the general population?

PPTC7 p.Gly35Val (c.104G>T) is no allele count reported in gnomAD v4.1 (AN 1,547,862) (gnomAD).

What do computational predictors say about PPTC7 p.Gly35Val (c.104G>T)?

AlphaMissense predicts likely benign (score 0.1653) — an in-silico prediction, not a clinical call.

PPTC7 p.Gly35Val

c.104G>T · VCV3937427

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1653 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,547,862)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1653	likely benign
REVEL	0.097	moderately benign-leaning
SaProt	LLR -5.39	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.6	GERP 1.3, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 46 kb · p 1.6e-20 · regional, not allelic
Overall
CADD	19.48	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

No allele count reported in gnomAD v4.1 (AN 1,547,862). 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: PPTC7
Protein: p.Gly35Val
Coding: c.104G>T
MANE Select: NM_139283
Type: single nucleotide variant
Location: chr12:110582928 (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.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-gly35val (accessed [today's date]).

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