Is PHKB p.Leu45Pro (c.134T>C) pathogenic?

PHKB p.Leu45Pro (c.134T>C) is classified Uncertain significance in PHKB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-08). AlphaMissense: likely benign (0.2054); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PHKB p.Leu45Pro (c.134T>C)?

PHKB p.Leu45Pro (c.134T>C) is associated with Inborn genetic diseases (ClinVar).

How common is PHKB p.Leu45Pro (c.134T>C) in the general population?

PHKB p.Leu45Pro (c.134T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PHKB p.Leu45Pro (c.134T>C)?

AlphaMissense predicts likely benign (score 0.2054) — an in-silico prediction, not a clinical call.

PHKB p.Leu45Pro

c.134T>C · rs762053276 · VCV2306042

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2054 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,609,572)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2054	likely benign
REVEL	0.732	pathogenic-leaning
SaProt	LLR -6.92	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 0.52, phastCons 0.89
Regional constraint	o/e 0.98	unconstrained · MANE · 238 kb · p 0.5 · regional, not allelic
Overall
CADD	24.8	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

No allele count reported in gnomAD v4.1 (AN 1,609,572). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PHKB
Protein: p.Leu45Pro
Coding: c.134T>C
MANE Select: NM_000293
dbSNP: rs762053276
Type: single nucleotide variant
Location: chr16:47497456 (GRCh38)
Gene constraint: LOEUF 0.792 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 87.06 · 6 PDB
Residue 45: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PHKB p.Leu45Val Uncertain significance ★ ⚠ same residue
PHKB p.Leu45His Uncertain significance ★★ ⚠ same residue
PHKB p.Ala1072Thr Uncertain significance ★★ ⚠ same condition
PHKB p.Ala781Val Uncertain significance ★★ ⚠ same condition
PHKB p.Ala787Pro Uncertain significance ★★ ⚠ same condition
PHKB p.Ala9Thr Uncertain significance ★★ ⚠ same condition
PHKB p.Arg103Gln Uncertain significance ★★ ⚠ same condition
PHKB p.Arg131His Uncertain significance ★★ ⚠ same condition

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/phkb-p-leu45pro (accessed [today's date]).

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