Is PPIF p.Gly89Ser (c.265G>A) pathogenic?

PPIF p.Gly89Ser (c.265G>A) is classified Uncertain significance in PPIF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-04). AlphaMissense: likely pathogenic (0.6276); Very rare (popmax 0.00983%, nfe).

How common is PPIF p.Gly89Ser (c.265G>A) in the general population?

PPIF p.Gly89Ser (c.265G>A) is very rare (popmax 0.00983%, nfe) (gnomAD).

What do computational predictors say about PPIF p.Gly89Ser (c.265G>A)?

AlphaMissense predicts likely pathogenic (score 0.6276) — an in-silico prediction, not a clinical call.

PPIF p.Gly89Ser

c.265G>A · rs145899672 · VCV3217197

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6276 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00983%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.6276	likely pathogenic
REVEL	0.614	indeterminate
SaProt	LLR -12.68	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 6,290 bp · p 0.79 · regional, not allelic
Overall
CADD	32.0	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 0.00983% European (non-Finnish) · 116/1,180,016 alleles

Filtering AF 0.00834% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00776%

Overall 0.00768% 124/1,613,776 alleles · very rare exomes 110/1,461,576 · genomes 14/152,200 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00983%	10,173
Admixed American	0.00833%	12,003
East Asian	0.00223%	44,898
Remaining individualsnot grpmax-eligible	0.0016%	62,468
African / African-American	0.00134%	74,906

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: PPIF
Protein: p.Gly89Ser
Coding: c.265G>A
MANE Select: NM_005729
dbSNP: rs145899672
Type: single nucleotide variant
Location: chr10:79349703 (GRCh38)
Gene constraint: LOEUF 1.725 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.87 · 72 PDB
Residue 89: the ppiase cyclophilin-type domain

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

Similar variants

PPIF p.Arg124Cys Uncertain significance ★ ⚠ same type
PPIF p.Asp108Asn Uncertain significance ★ ⚠ same type
PPIF p.Asp162Gly Uncertain significance ★ ⚠ same type
PPIF p.Glu128Lys Uncertain significance ★ ⚠ same type
PPIF p.Gly117Arg Uncertain significance ★ ⚠ same type
PPIF p.Gly92Ala Uncertain significance ★ ⚠ same type
PPIF p.Lys160Arg Uncertain significance ★ ⚠ same type
PPIF p.Lys160Glu 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/ppif-p-gly89ser (accessed [today's date]).

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