Is IPMK p.Pro48Ser (c.142C>T) pathogenic?

IPMK p.Pro48Ser (c.142C>T) is classified Uncertain significance in IPMK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-12). AlphaMissense: likely pathogenic (0.9491); Very rare (popmax 0.00223%, eas).

How common is IPMK p.Pro48Ser (c.142C>T) in the general population?

IPMK p.Pro48Ser (c.142C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about IPMK p.Pro48Ser (c.142C>T)?

AlphaMissense predicts likely pathogenic (score 0.9491) — an in-silico prediction, not a clinical call.

IPMK p.Pro48Ser

c.142C>T · VCV3529567

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9491 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9491	likely pathogenic
REVEL	0.149	moderately benign-leaning
SaProt	LLR -9.04	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP -0.51, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 30 kb · p 0.27 · regional, not allelic
Overall
CADD	26.5	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 0.00223% East Asian · 1/44,876 alleles

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

Overall 0.000186% 3/1,613,550 alleles · very rare exomes 2/1,461,318 · genomes 1/152,232 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,876
European (non-Finnish)	0.00017%	589,943

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.Pro48Ser
Coding: c.142C>T
MANE Select: NM_152230
Type: single nucleotide variant
Location: chr10:58267470 (GRCh38)
Gene constraint: LOEUF 0.6 · pLI 0.82 (gnomAD)
Structure: AlphaFold pLDDT 74.50 · 25 PDB

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-pro48ser (accessed [today's date]).

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