Is PIR p.His237Pro (c.710A>C) pathogenic?

PIR p.His237Pro (c.710A>C) is classified Uncertain significance in PIR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-11). AlphaMissense: likely pathogenic (0.8911); Absent from gnomAD v4.1.

How common is PIR p.His237Pro (c.710A>C) in the general population?

PIR p.His237Pro (c.710A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PIR p.His237Pro (c.710A>C)?

AlphaMissense predicts likely pathogenic (score 0.8911) — an in-silico prediction, not a clinical call.

PIR p.His237Pro

c.710A>C · VCV3418789

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8911 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8911	likely pathogenic
REVEL	0.343	indeterminate
SaProt	LLR -13.37	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 2.6, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 106 kb · p 0.98 · regional, not allelic
Overall
CADD	23.4	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: PIR
Protein: p.His237Pro
Coding: c.710A>C
MANE Select: NM_001018109
Type: single nucleotide variant
Location: chrX:15390235 (GRCh38)
Structure: AlphaFold pLDDT 97.11 · 13 PDB
Residue 237: a β-strand

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

Similar variants

PIR p.Asp232Asn Benign ★★ same type
PIR p.Val228Ala Benign ★★ same type
PIR p.Ala274Thr Uncertain significance ★ ⚠ same type
PIR p.Arg14Gln Uncertain significance ★ ⚠ same type
PIR p.Arg25Gln Uncertain significance ★ ⚠ same type
PIR p.Arg97Gln Uncertain significance ★ ⚠ same type
PIR p.Asn273Asp Uncertain significance ★ ⚠ same type
PIR p.Asp145Asn 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/pir-p-his237pro (accessed [today's date]).

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