Is IPMK p.Thr3Ala (c.7A>G) pathogenic?

IPMK p.Thr3Ala (c.7A>G) is classified Uncertain significance in IPMK (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-17). AlphaMissense: likely benign (0.0729); Very rare (popmax 0.00268%, afr).

How common is IPMK p.Thr3Ala (c.7A>G) in the general population?

IPMK p.Thr3Ala (c.7A>G) is very rare (popmax 0.00268%, afr) (gnomAD).

What do computational predictors say about IPMK p.Thr3Ala (c.7A>G)?

AlphaMissense predicts likely benign (score 0.0729) — an in-silico prediction, not a clinical call.

IPMK p.Thr3Ala

c.7A>G · rs1011521364 · VCV2251778

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0729 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00268%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0729	likely benign
REVEL	0.021	moderately benign-leaning
SaProt	LLR -4.92	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 2.2	GERP -0.017, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 30 kb · p 0.27 · regional, not allelic
Overall
CADD	17.47	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 0.00268% African / African-American · 2/74,514 alleles

Filtering AF 0.000445% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000167%

Overall 0.000627% 10/1,596,102 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00268%	37,257
East Asian	0.00227%	44,140
European (non-Finnish)	0.000598%	167,350

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.Thr3Ala
Coding: c.7A>G
MANE Select: NM_152230
dbSNP: rs1011521364
Type: single nucleotide variant
Location: chr10:58267605 (GRCh38)
Gene constraint: LOEUF 0.6 · pLI 0.82 (gnomAD)
Structure: AlphaFold pLDDT 74.50 · 25 PDB
Residue 3: the 'disordered' region

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-thr3ala (accessed [today's date]).

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