Is PITPNB p.Pro172Arg (c.515C>G) pathogenic?

PITPNB p.Pro172Arg (c.515C>G) is classified Uncertain significance in PITPNB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-14). AlphaMissense: ambiguous (0.4864); Absent from gnomAD v4.1.

How common is PITPNB p.Pro172Arg (c.515C>G) in the general population?

PITPNB p.Pro172Arg (c.515C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PITPNB p.Pro172Arg (c.515C>G)?

AlphaMissense predicts ambiguous (score 0.4864) — an in-silico prediction, not a clinical call.

PITPNB p.Pro172Arg

c.515C>G · VCV4137183

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4864 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4864	ambiguous
REVEL	0.453	indeterminate
SaProt	LLR -6.72	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 64 kb · p 4.6e-15 · regional, not allelic
Overall
CADD	28.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PITPNB
Protein: p.Pro172Arg
Coding: c.515C>G
MANE Select: NM_012399
Type: single nucleotide variant
Location: chr22:27873757 (GRCh38)
Gene constraint: LOEUF 1.807 · pLI 0.22 (gnomAD)
Structure: AlphaFold pLDDT 95.59
Residue 172: the pitp-like domain

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

Similar variants

PITPNB c.20+71G>A Uncertain significance ★ same type
PITPNB p.Ala90Val Uncertain significance ★ ⚠ same type
PITPNB p.Asp159Tyr Uncertain significance ★ ⚠ same type
PITPNB p.Cys187Tyr Uncertain significance ★ ⚠ same type
PITPNB p.Gln16Arg Uncertain significance ★ ⚠ same type
PITPNB p.His84Gln Uncertain significance ★ ⚠ same type
PITPNB p.Ile111Val Uncertain significance ★ ⚠ same type
PITPNB p.Lys50Thr 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/pitpnb-p-pro172arg (accessed [today's date]).

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