Is PPIL4 p.Val271Ile (c.811G>A) pathogenic?

PPIL4 p.Val271Ile (c.811G>A) is classified Uncertain significance in PPIL4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-05). AlphaMissense: likely benign (0.1157); No allele count reported in gnomAD v4.1 (AN 1,517,606).

How common is PPIL4 p.Val271Ile (c.811G>A) in the general population?

PPIL4 p.Val271Ile (c.811G>A) is no allele count reported in gnomAD v4.1 (AN 1,517,606) (gnomAD).

What do computational predictors say about PPIL4 p.Val271Ile (c.811G>A)?

AlphaMissense predicts likely benign (score 0.1157) — an in-silico prediction, not a clinical call.

PPIL4 p.Val271Ile

c.811G>A · rs1188739586 · VCV3217225

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1157 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,517,606)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1157	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -6.14	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.4, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 41 kb · p 8.5e-06 · regional, not allelic
Overall
CADD	22.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

No allele count reported in gnomAD v4.1 (AN 1,517,606). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PPIL4
Protein: p.Val271Ile
Coding: c.811G>A
MANE Select: NM_139126
dbSNP: rs1188739586
Type: single nucleotide variant
Location: chr6:149525202 (GRCh38)
Gene constraint: LOEUF 1.088 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.56 · 7 PDB
Residue 271: the rrm domain

Full PPIL4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PPIL4 p.Ala297Thr Uncertain significance ★ ⚠ same type
PPIL4 p.Arg437Gln Uncertain significance ★ ⚠ same type
PPIL4 p.Arg445Gln Uncertain significance ★ ⚠ same type
PPIL4 p.Arg476Gln Uncertain significance ★ ⚠ same type
PPIL4 p.Arg476Pro Uncertain significance ★ ⚠ same type
PPIL4 p.Arg61Cys Uncertain significance ★ ⚠ same type
PPIL4 p.Asn240Tyr Uncertain significance ★ ⚠ same type
PPIL4 p.Asn38Asp 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/ppil4-p-val271ile (accessed [today's date]).

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