Is PPTC7 p.Ile116Thr (c.347T>C) pathogenic?

PPTC7 p.Ile116Thr (c.347T>C) is classified Uncertain significance in PPTC7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-08). AlphaMissense: likely benign (0.096); Ultra-rare (popmax 0.0922%, sas).

How common is PPTC7 p.Ile116Thr (c.347T>C) in the general population?

PPTC7 p.Ile116Thr (c.347T>C) is ultra-rare (popmax 0.0922%, sas) (gnomAD).

What do computational predictors say about PPTC7 p.Ile116Thr (c.347T>C)?

AlphaMissense predicts likely benign (score 0.096) — an in-silico prediction, not a clinical call.

PPTC7 p.Ile116Thr

c.347T>C · rs147203978 · VCV3217976

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.096 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0922%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.096	likely benign
REVEL	0.181	moderately benign-leaning
SaProt	LLR -5.63	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 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 46 kb · p 1.6e-20 · regional, not allelic
Overall
CADD	22.9	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 0.0922% South Asian · 84/91,088 alleles

Filtering AF 0.0763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0704%

Overall 0.00892% 144/1,614,074 alleles · ultra-rare exomes 138/1,461,872 · genomes 6/152,202 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0922%	1,084
Middle Eastern	0.0493%	2,028
Remaining individualsnot grpmax-eligible	0.0064%	15,622
European (non-Finnish)	0.00441%	22,693
African / African-American	0.00133%	74,934

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.Ile116Thr
Coding: c.347T>C
MANE Select: NM_139283
dbSNP: rs147203978
Type: single nucleotide variant
Location: chr12:110551845 (GRCh38)
Gene constraint: LOEUF 0.421 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 88.84
Residue 116: 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-ile116thr (accessed [today's date]).

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