Is PPIF p.Arg124Cys (c.370C>T) pathogenic?

PPIF p.Arg124Cys (c.370C>T) is classified Uncertain significance in PPIF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-23). AlphaMissense: likely benign (0.3313); Ultra-rare (popmax 0.0165%, mid).

How common is PPIF p.Arg124Cys (c.370C>T) in the general population?

PPIF p.Arg124Cys (c.370C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about PPIF p.Arg124Cys (c.370C>T)?

AlphaMissense predicts likely benign (score 0.3313) — an in-silico prediction, not a clinical call.

PPIF p.Arg124Cys

c.370C>T · rs779687777 · VCV3217199

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3313 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3313	likely benign
REVEL	0.301	indeterminate
SaProt	LLR -13.62	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 0.44, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 6,290 bp · p 0.79 · regional, not allelic
Overall
CADD	29.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,060 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00228%

Overall 0.00124% 20/1,614,118 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,060
African / African-American	0.00799%	12,510
Admixed American	0.00666%	15,006
South Asian	0.00549%	18,215
East Asian	0.00446%	22,437
European (non-Finnish)	0.000169%	589,995

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.Arg124Cys
Coding: c.370C>T
MANE Select: NM_005729
dbSNP: rs779687777
Type: single nucleotide variant
Location: chr10:79351541 (GRCh38)
Gene constraint: LOEUF 1.725 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.87 · 72 PDB
Residue 124: the ppiase cyclophilin-type domain

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

Similar variants

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
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-arg124cys (accessed [today's date]).

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