Is PHKB p.Ser794Phe (c.2381C>T) pathogenic?

PHKB p.Ser794Phe (c.2381C>T) is classified Uncertain significance in PHKB (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-09). AlphaMissense: ambiguous (0.5598); Very rare (popmax 0.0011%, sas); Associated with Inborn genetic diseases.

What condition is associated with PHKB p.Ser794Phe (c.2381C>T)?

PHKB p.Ser794Phe (c.2381C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PHKB p.Ser794Phe (c.2381C>T) in the general population?

PHKB p.Ser794Phe (c.2381C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about PHKB p.Ser794Phe (c.2381C>T)?

AlphaMissense predicts ambiguous (score 0.5598) — an in-silico prediction, not a clinical call.

PHKB p.Ser794Phe

c.2381C>T · VCV4839152

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5598 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5598	ambiguous
REVEL	0.604	indeterminate
SaProt	LLR -8.32	tolerated
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.6	GERP 2.6, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 238 kb · p 0.5 · regional, not allelic
Overall
CADD	27.9	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 0.0011% South Asian · 1/91,052 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000744% 12/1,613,808 alleles · very rare exomes 12/1,461,538 · genomes 0/152,270 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,052
European (non-Finnish)	0.000932%	107,254

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: PHKB
Protein: p.Ser794Phe
Coding: c.2381C>T
MANE Select: NM_000293
Type: single nucleotide variant
Location: chr16:47664929 (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 794: the 'calmodulin-binding' region

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.Ser794= Likely benign ★ 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
PHKB p.Arg144Cys 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-ser794phe (accessed [today's date]).

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