Is PPIF p.Val71Ile (c.211G>A) pathogenic?

PPIF p.Val71Ile (c.211G>A) is classified Uncertain significance in PPIF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-15). AlphaMissense: ambiguous (0.5534); Rare (popmax 0.148%, mid).

How common is PPIF p.Val71Ile (c.211G>A) in the general population?

PPIF p.Val71Ile (c.211G>A) is rare (popmax 0.148%, mid) (gnomAD).

What do computational predictors say about PPIF p.Val71Ile (c.211G>A)?

AlphaMissense predicts ambiguous (score 0.5534) — an in-silico prediction, not a clinical call.

PPIF p.Val71Ile

c.211G>A · rs371203826 · VCV2289697

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5534 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.148%, mid)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5534	ambiguous
REVEL	0.192	benign-leaning
SaProt	LLR -9.85	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 6,290 bp · p 0.79 · regional, not allelic
Overall
CADD	27.3	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 0.148% Middle Eastern · 9/6,082 alleles

Filtering AF 0.0772% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0577%

Overall 0.0039% 63/1,613,860 alleles · rare exomes 58/1,461,646 · genomes 5/152,214 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.148%	676
South Asian	0.00439%	22,773
European (non-Finnish)	0.00398%	25,106
Admixed American	0.00167%	60,012
Remaining individualsnot grpmax-eligible	0.0016%	62,474
African / African-American	0.00133%	74,922

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.Val71Ile
Coding: c.211G>A
MANE Select: NM_005729
dbSNP: rs371203826
Type: single nucleotide variant
Location: chr10:79349091 (GRCh38)
Gene constraint: LOEUF 1.725 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.87 · 72 PDB
Residue 71: 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-val71ile (accessed [today's date]).

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