Is PPIC p.Thr107Pro (c.319A>C) pathogenic?

PPIC p.Thr107Pro (c.319A>C) is classified Uncertain significance in PPIC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-12). AlphaMissense: likely pathogenic (0.8308); Ultra-rare (popmax 0.0441%, sas).

How common is PPIC p.Thr107Pro (c.319A>C) in the general population?

PPIC p.Thr107Pro (c.319A>C) is ultra-rare (popmax 0.0441%, sas) (gnomAD).

What do computational predictors say about PPIC p.Thr107Pro (c.319A>C)?

AlphaMissense predicts likely pathogenic (score 0.8308) — an in-silico prediction, not a clinical call.

PPIC p.Thr107Pro

c.319A>C · VCV3423519

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8308 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0441%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8308	likely pathogenic
REVEL	0.361	indeterminate
SaProt	LLR -15.50	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.2, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 13 kb · p 0.97 · regional, not allelic
Overall
CADD	27.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0441% South Asian · 40/90,784 alleles

Filtering AF 0.0332% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0294%

Overall 0.00261% 42/1,611,316 alleles · ultra-rare exomes 37/1,458,972 · genomes 5/152,344 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0441%	2,270
Remaining individualsnot grpmax-eligible	0.0016%	62,408
European (non-Finnish)	8.49e-05%	1,177,970

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: PPIC
Protein: p.Thr107Pro
Coding: c.319A>C
MANE Select: NM_000943
Type: single nucleotide variant
Location: chr5:123028781 (GRCh38)
Gene constraint: LOEUF 1.354 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.88 · 1 PDB
Residue 107: the ppiase cyclophilin-type domain; a β-strand

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

Similar variants

PPIC p.Ala137Thr Uncertain significance ★ ⚠ same type
PPIC p.Ala19Val Uncertain significance ★ ⚠ same type
PPIC p.Ala210Thr Uncertain significance ★ ⚠ same type
PPIC p.Arg6Gln Uncertain significance ★ ⚠ same type
PPIC p.Asp185Glu Uncertain significance ★ ⚠ same type
PPIC p.Asp200Gly Uncertain significance ★ ⚠ same type
PPIC p.Glu115Asp Uncertain significance ★ ⚠ same type
PPIC p.Gly130Glu 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/ppic-p-thr107pro (accessed [today's date]).

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