Is IPMK p.Asn138Ile (c.413A>T) pathogenic?

IPMK p.Asn138Ile (c.413A>T) is classified Uncertain significance in IPMK (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-21). AlphaMissense: likely benign (0.1094); Ultra-rare (popmax 0.0491%, afr).

How common is IPMK p.Asn138Ile (c.413A>T) in the general population?

IPMK p.Asn138Ile (c.413A>T) is ultra-rare (popmax 0.0491%, afr) (gnomAD).

What do computational predictors say about IPMK p.Asn138Ile (c.413A>T)?

AlphaMissense predicts likely benign (score 0.1094) — an in-silico prediction, not a clinical call.

IPMK p.Asn138Ile

c.413A>T · rs145577988 · VCV2377001

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1094 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0491%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1094	likely benign
REVEL	0.041	moderately benign-leaning
SaProt	LLR -3.75	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	GERP -3.4, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 42 kb · p 3.5e-08 · regional, not allelic
Overall
CADD	17.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0491% African / African-American · 36/73,362 alleles

Filtering AF 0.0364% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.032%

Overall 0.00246% 39/1,588,190 alleles · ultra-rare exomes 15/1,436,012 · genomes 24/152,178 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0491%	2,038
Admixed American	0.00353%	28,305
European (non-Finnish)	8.57e-05%	1,166,378

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.Asn138Ile
Coding: c.413A>T
MANE Select: NM_152230
dbSNP: rs145577988
Type: single nucleotide variant
Location: chr10:58216278 (GRCh38)
Gene constraint: LOEUF 0.6 · pLI 0.82 (gnomAD)
Structure: AlphaFold pLDDT 74.50 · 25 PDB
Residue 138: 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-asn138ile (accessed [today's date]).

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