Is ITPKB p.Ser600Phe (c.1799C>T) pathogenic?

ITPKB p.Ser600Phe (c.1799C>T) is classified Uncertain significance in ITPKB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-02). AlphaMissense: likely pathogenic (0.8042); Very rare (popmax 8.48e-05%, nfe).

How common is ITPKB p.Ser600Phe (c.1799C>T) in the general population?

ITPKB p.Ser600Phe (c.1799C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about ITPKB p.Ser600Phe (c.1799C>T)?

AlphaMissense predicts likely pathogenic (score 0.8042) — an in-silico prediction, not a clinical call.

ITPKB p.Ser600Phe

c.1799C>T · rs2464943244 · VCV3111703

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8042 · ACMG-weighted

gnomAD v4.1

Rare

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

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8042	likely pathogenic
REVEL	0.292	indeterminate
SaProt	LLR -7.23	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 1,929 bp · p 2.3e-06 · regional, not allelic
Overall
CADD	32.0	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 8.48e-05% European (non-Finnish) · 1/1,178,740 alleles

Overall 6.2e-05% 1/1,611,828 alleles · very rare exomes 1/1,459,548 · genomes 0/152,280 · 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: ITPKB
Protein: p.Ser600Phe
Coding: c.1799C>T
MANE Select: NM_002221
dbSNP: rs2464943244
Type: single nucleotide variant
Location: chr1:226735660 (GRCh38)
Gene constraint: LOEUF 0.34 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.58
Residue 600: the 'disordered' region

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

Similar variants

ITPKB p.Glu906Gln Uncertain significance ★★ ⚠ same type
ITPKB p.Pro358Ser Uncertain significance ★★ ⚠ same type
ITPKB p.Pro415His Uncertain significance ★★ ⚠ same type
ITPKB p.Thr757Ala Uncertain significance ★★ ⚠ same type
ITPKB c.-8C>T Benign ★★ same type
ITPKB p.Ala632= Benign ★★ same type
ITPKB p.Asn592= Benign ★★ same type
ITPKB p.Asp320Ala Benign/Likely benign ★★ 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/itpkb-p-ser600phe (accessed [today's date]).

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