Is PITPNB p.Phe71Ser (c.212T>C) pathogenic?

PITPNB p.Phe71Ser (c.212T>C) is classified Uncertain significance in PITPNB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-15). AlphaMissense: likely pathogenic (0.9397); Absent from gnomAD v4.1.

How common is PITPNB p.Phe71Ser (c.212T>C) in the general population?

PITPNB p.Phe71Ser (c.212T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PITPNB p.Phe71Ser (c.212T>C)?

AlphaMissense predicts likely pathogenic (score 0.9397) — an in-silico prediction, not a clinical call.

PITPNB p.Phe71Ser

c.212T>C · VCV3418803

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9397 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9397	likely pathogenic
REVEL	0.663	pathogenic-leaning
SaProt	LLR -13.68	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 11	GERP 2.8, phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 64 kb · p 4.6e-15 · regional, not allelic
Overall
CADD	29.6	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

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.Phe71Ser
Coding: c.212T>C
MANE Select: NM_012399
Type: single nucleotide variant
Location: chr22:27897878 (GRCh38)
Gene constraint: LOEUF 1.807 · pLI 0.22 (gnomAD)
Structure: AlphaFold pLDDT 95.59
Residue 71: 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-phe71ser (accessed [today's date]).

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