Is IPMK p.Thr28Ala (c.82A>G) pathogenic?

IPMK p.Thr28Ala (c.82A>G) is classified Likely benign in IPMK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-25). AlphaMissense: likely benign (0.0548); Low-frequency (popmax 1.32%, mid).

How common is IPMK p.Thr28Ala (c.82A>G) in the general population?

IPMK p.Thr28Ala (c.82A>G) is low-frequency (popmax 1.32%, mid) (gnomAD).

What do computational predictors say about IPMK p.Thr28Ala (c.82A>G)?

AlphaMissense predicts likely benign (score 0.0548) — an in-silico prediction, not a clinical call.

IPMK p.Thr28Ala

c.82A>G · VCV4907482

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0548 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.32%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0548	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -5.74	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 -0.035	GERP -2.1, phastCons 0.077
Regional constraint	o/e 1.11	unconstrained · MANE · 30 kb · p 0.27 · regional, not allelic
Overall
CADD	10.74	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 1.32% Middle Eastern · 79/5,964 alleles

Filtering AF 1.09% ClinGen BA1/BS1 input FAF95, joint · FAF99 1%

Overall 0.0442% 713/1,612,548 alleles · low-frequency exomes 625/1,460,544 · genomes 88/152,004 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	1.32%	75
Admixed American	0.207%	483
Ashkenazi Jewishnot grpmax-eligible	0.162%	616
Remaining individualsnot grpmax-eligible	0.0994%	1,006
European (non-Finnish)	0.0309%	3,232
South Asian	0.0264%	3,791
African / African-American	0.0147%	6,809

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.Thr28Ala
Coding: c.82A>G
MANE Select: NM_152230
Type: single nucleotide variant
Location: chr10:58267530 (GRCh38)
Gene constraint: LOEUF 0.6 · pLI 0.82 (gnomAD)
Structure: AlphaFold pLDDT 74.50 · 25 PDB
Residue 28: 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-thr28ala (accessed [today's date]).

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