Is IRF2BP2 p.Val41= (c.123C>T) pathogenic?

IRF2BP2 p.Val41= (c.123C>T) is classified Likely benign in IRF2BP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-14). Ultra-rare (popmax 0.046%, sas).

How common is IRF2BP2 p.Val41= (c.123C>T) in the general population?

IRF2BP2 p.Val41= (c.123C>T) is ultra-rare (popmax 0.046%, sas) (gnomAD).

IRF2BP2 p.Val41=

c.123C>T · rs543187746 · VCV1544998

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.046%, sas)

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 3.6	GERP -1.8, phastCons 1
Overall
CADD	10.84	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.046% South Asian · 39/84,744 alleles

Filtering AF 0.0345% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0306%

Overall 0.00328% 51/1,554,122 alleles · ultra-rare exomes 47/1,402,648 · genomes 4/151,474 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.046%	2,173
Remaining individualsnot grpmax-eligible	0.00334%	29,905
European (non-Finnish)	0.000867%	115,280

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.Val41=
Coding: c.123C>T
MANE Select: NM_182972
dbSNP: rs543187746
Type: single nucleotide variant
Location: chr1:234609372 (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.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
IRF2BP2 p.Ala344Val Uncertain significance ★★ ⚠ same type
IRF2BP2 p.Ala502Ser 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-val41 (accessed [today's date]).

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