Is IREB2 p.Ser332= (c.996C>T) pathogenic?

IREB2 p.Ser332= (c.996C>T) is classified Likely benign in IREB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-23). Rare (popmax 0.105%, afr).

How common is IREB2 p.Ser332= (c.996C>T) in the general population?

IREB2 p.Ser332= (c.996C>T) is rare (popmax 0.105%, afr) (gnomAD).

IREB2 p.Ser332=

c.996C>T · rs115884650 · VCV2143548

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.105%, afr)

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 1.4	GERP 1.1, phastCons 1
Overall
CADD	12.43	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.105% African / African-American · 79/74,988 alleles

Filtering AF 0.0866% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0797%

Overall 0.0062% 100/1,613,522 alleles · rare exomes 57/1,461,302 · genomes 43/152,220 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.105%	949
Remaining individualsnot grpmax-eligible	0.0208%	4,807
Admixed American	0.0117%	8,572
European (non-Finnish)	8.48e-05%	1,179,528

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: IREB2
Protein: p.Ser332=
Coding: c.996C>T
MANE Select: NM_004136
dbSNP: rs115884650
Type: single nucleotide variant
Location: chr15:78473354 (GRCh38)
Gene constraint: LOEUF 0.389 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.11 · 1 PDB
Residue 332: an α-helix

Full IREB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IREB2 p.Ala534Thr Uncertain significance ★★ ⚠ same type
IREB2 p.Arg697Trp Uncertain significance ★★ ⚠ same type
IREB2 p.Asn925Thr Uncertain significance ★★ ⚠ same type
IREB2 p.Cys53Tyr Uncertain significance ★★ same type
IREB2 p.Glu917Lys Uncertain significance ★★ ⚠ same type
IREB2 p.Gly184Asp Uncertain significance ★★ ⚠ same type
IREB2 p.Gly656Ser Uncertain significance ★★ ⚠ same type
IREB2 p.His22Leu 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/ireb2-p-ser332 (accessed [today's date]).

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