Is IPMK p.Ala250Thr (c.748G>A) pathogenic?

IPMK p.Ala250Thr (c.748G>A) is classified Uncertain significance in IPMK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-01). AlphaMissense: likely pathogenic (0.9827); Very rare (popmax 0.00133%, afr).

How common is IPMK p.Ala250Thr (c.748G>A) in the general population?

IPMK p.Ala250Thr (c.748G>A) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about IPMK p.Ala250Thr (c.748G>A)?

AlphaMissense predicts likely pathogenic (score 0.9827) — an in-silico prediction, not a clinical call.

IPMK p.Ala250Thr

c.748G>A · VCV3286297

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9827 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9827	likely pathogenic
REVEL	0.32	indeterminate
SaProt	LLR -4.27	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 42 kb · p 3.5e-08 · regional, not allelic
Overall
CADD	27.8	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 0.00133% African / African-American · 1/75,024 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000205% 3/1,461,764 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,024
European (non-Finnish)	0.000169%	590,002

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.Ala250Thr
Coding: c.748G>A
MANE Select: NM_152230
Type: single nucleotide variant
Location: chr10:58196579 (GRCh38)
Gene constraint: LOEUF 0.6 · pLI 0.82 (gnomAD)
Structure: AlphaFold pLDDT 74.50 · 25 PDB
Residue 250: 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.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
IPMK p.Asn138Ile 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-ala250thr (accessed [today's date]).

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