Is PPIF p.Ser93Phe (c.278C>T) pathogenic?

PPIF p.Ser93Phe (c.278C>T) is classified Uncertain significance in PPIF (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-13). AlphaMissense: likely pathogenic (0.9791); Ultra-rare (popmax 0.0535%, eas).

How common is PPIF p.Ser93Phe (c.278C>T) in the general population?

PPIF p.Ser93Phe (c.278C>T) is ultra-rare (popmax 0.0535%, eas) (gnomAD).

What do computational predictors say about PPIF p.Ser93Phe (c.278C>T)?

AlphaMissense predicts likely pathogenic (score 0.9791) — an in-silico prediction, not a clinical call.

PPIF p.Ser93Phe

c.278C>T · rs780132922 · VCV2536982

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9791 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0535%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9791	likely pathogenic
REVEL	0.906	moderately pathogenic-leaning
SaProt	LLR -13.30	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 2.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 6,290 bp · p 0.79 · regional, not allelic
Overall
CADD	30.0	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 0.0535% East Asian · 24/44,898 alleles

Filtering AF 0.0368% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0313%

Overall 0.00155% 25/1,613,876 alleles · ultra-rare exomes 24/1,461,652 · genomes 1/152,224 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0535%	1,871
Admixed American	0.00167%	60,012

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.Ser93Phe
Coding: c.278C>T
MANE Select: NM_005729
dbSNP: rs780132922
Type: single nucleotide variant
Location: chr10:79349716 (GRCh38)
Gene constraint: LOEUF 1.725 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.87 · 72 PDB
Residue 93: 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.Gly89Ser Uncertain significance ★ ⚠ same type
PPIF p.Gly92Ala Uncertain significance ★ ⚠ same type
PPIF p.Lys160Arg 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-ser93phe (accessed [today's date]).

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