Is IPMK p.Leu66= (c.198G>T) pathogenic?

IPMK p.Leu66= (c.198G>T) is classified Likely benign in IPMK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-28). Rare (popmax 0.866%, sas).

How common is IPMK p.Leu66= (c.198G>T) in the general population?

IPMK p.Leu66= (c.198G>T) is rare (popmax 0.866%, sas) (gnomAD).

IPMK p.Leu66=

c.198G>T · VCV4907481

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.866%, 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 0.38	GERP -1.9, phastCons 0.99
Overall
CADD	5.738	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.866% South Asian · 788/91,040 alleles

Filtering AF 0.815% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.795%

Overall 0.0529% 853/1,612,772 alleles · rare exomes 819/1,460,470 · genomes 34/152,302 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.866%	116
Remaining individualsnot grpmax-eligible	0.0881%	1,136
Middle Eastern	0.0333%	3,006
East Asian	0.00892%	11,213
African / African-American	0.00133%	74,988
European (non-Finnish)	0.000254%	392,961

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: IPMK
Protein: p.Leu66=
Coding: c.198G>T
MANE Select: NM_152230
Type: single nucleotide variant
Location: chr10:58237807 (GRCh38)
Gene constraint: LOEUF 0.6 · pLI 0.82 (gnomAD)
Structure: AlphaFold pLDDT 74.50 · 25 PDB
Residue 66: a β-strand

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

Similar variants

IPMK p.Asn124= Benign ★★ same type
IPMK p.Thr32= Benign ★★ same type
IPMK p.Ala228Val Uncertain significance ★ ⚠ same type
IPMK p.Ala250Thr Uncertain significance ★ ⚠ same type
IPMK p.Ala319Val Uncertain significance ★ ⚠ same type
IPMK p.Arg10Gln Uncertain significance ★ ⚠ same type
IPMK p.Arg10Trp Uncertain significance ★ ⚠ same type
IPMK p.Arg320His 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/ipmk-p-leu66 (accessed [today's date]).

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