Is IRF2BP2 p.Pro329= (c.987G>A) pathogenic?

IRF2BP2 p.Pro329= (c.987G>A) is classified Likely benign in IRF2BP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-26). Very rare (popmax 8.49e-05%, nfe).

How common is IRF2BP2 p.Pro329= (c.987G>A) in the general population?

IRF2BP2 p.Pro329= (c.987G>A) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

IRF2BP2 p.Pro329=

c.987G>A · VCV3715170

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.007	GERP -0.11, phastCons 0.14
Overall
CADD	11.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.49e-05% European (non-Finnish) · 1/1,178,492 alleles

Overall 6.21e-05% 1/1,609,826 alleles · very rare exomes 1/1,457,468 · genomes 0/152,358 · joint denominator

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: IRF2BP2
Protein: p.Pro329=
Coding: c.987G>A
MANE Select: NM_182972
Type: single nucleotide variant
Location: chr1:234608508 (GRCh38)
Gene constraint: LOEUF 0.709 · pLI 0.41 (gnomAD)
Structure: AlphaFold pLDDT 56.84 · 3 PDB

Full IRF2BP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IRF2BP2 p.Pro329Ala Uncertain significance ★ ⚠ same residue
IRF2BP2 p.Pro329Ser Uncertain significance ★ ⚠ same residue
IRF2BP2 p.Ala143Gly Uncertain significance ★★ ⚠ same type
IRF2BP2 p.Ala209Gly Uncertain significance ★★ ⚠ same type
IRF2BP2 p.Ala214Thr Uncertain significance ★★ ⚠ same type
IRF2BP2 p.Ala246Val Uncertain significance ★★ ⚠ same type
IRF2BP2 p.Ala254Thr Uncertain significance ★★ ⚠ same type
IRF2BP2 p.Ala276Thr 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/irf2bp2-p-pro329 (accessed [today's date]).

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