Is IKZF2 p.Ser32Arg (c.96C>G) pathogenic?

IKZF2 p.Ser32Arg (c.96C>G) is classified Uncertain significance in IKZF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-23). AlphaMissense: likely pathogenic (0.7317); Ultra-rare (popmax 0.0107%, afr).

How common is IKZF2 p.Ser32Arg (c.96C>G) in the general population?

IKZF2 p.Ser32Arg (c.96C>G) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

What do computational predictors say about IKZF2 p.Ser32Arg (c.96C>G)?

AlphaMissense predicts likely pathogenic (score 0.7317) — an in-silico prediction, not a clinical call.

IKZF2 p.Ser32Arg

c.96C>G · VCV4688963

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7317 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7317	likely pathogenic
REVEL	0.179	moderately benign-leaning
SaProt	LLR -6.82	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 92 kb · p 0.14 · regional, not allelic
Overall
CADD	27.2	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

Grpmax group 0.0107% African / African-American · 8/74,908 alleles

Filtering AF 0.00528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.000496% 8/1,613,880 alleles · ultra-rare exomes 2/1,461,730 · genomes 6/152,150 · 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: IKZF2
Protein: p.Ser32Arg
Coding: c.96C>G
MANE Select: NM_001387220
Type: single nucleotide variant
Location: chr2:213147751 (GRCh38)
Gene constraint: LOEUF 0.5 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 52.62 · 8 PDB
Residue 32: the 'disordered' region

Full IKZF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IKZF2 p.Ser209Asn Uncertain significance ★★ ⚠ same type
IKZF2 p.Asn93Ser Benign/Likely benign ★★ same type
IKZF2 p.Glu21= Benign ★★ same type
IKZF2 p.Pro340= Likely benign ★★ same type
IKZF2 c.575-8C>T Uncertain significance ★ same type
IKZF2 p.Arg138Cys Uncertain significance ★ ⚠ same type
IKZF2 p.Arg363Lys Uncertain significance ★ ⚠ same type
IKZF2 p.Arg388Lys 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/ikzf2-p-ser32arg (accessed [today's date]).

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