Is IP6K3 p.Met58Val (c.172A>G) pathogenic?

IP6K3 p.Met58Val (c.172A>G) is classified Uncertain significance in IP6K3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-06). AlphaMissense: likely benign (0.1256); Very rare (popmax 8.48e-05%, nfe).

How common is IP6K3 p.Met58Val (c.172A>G) in the general population?

IP6K3 p.Met58Val (c.172A>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about IP6K3 p.Met58Val (c.172A>G)?

AlphaMissense predicts likely benign (score 0.1256) — an in-silico prediction, not a clinical call.

IP6K3 p.Met58Val

c.172A>G · VCV4276109

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1256 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1256	likely benign
REVEL	0.307	indeterminate
SaProt	LLR -8.80	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP 0.13, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 13 kb · p 0.014 · regional, not allelic
Overall
CADD	19.1	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 8.48e-05% European (non-Finnish) · 1/1,179,338 alleles

Overall 6.2e-05% 1/1,612,040 alleles · very rare exomes 1/1,459,794 · genomes 0/152,246 · joint denominator

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: IP6K3
Protein: p.Met58Val
Coding: c.172A>G
MANE Select: NM_054111
Type: single nucleotide variant
Location: chr6:33735305 (GRCh38)
Gene constraint: LOEUF 1.028 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.40

Full IP6K3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IP6K3 p.Gly26Arg Uncertain significance ★★ ⚠ same type
IP6K3 p.Ala124Asp Uncertain significance ★ ⚠ same type
IP6K3 p.Ala129Val Uncertain significance ★ ⚠ same type
IP6K3 p.Ala233Pro Uncertain significance ★ ⚠ same type
IP6K3 p.Ala7Thr Uncertain significance ★ ⚠ same type
IP6K3 p.Ala9Val Uncertain significance ★ ⚠ same type
IP6K3 p.Arg133Ser Uncertain significance ★ ⚠ same type
IP6K3 p.Arg185Cys 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/ip6k3-p-met58val (accessed [today's date]).

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