Is PHKG1 p.Pro153Ser (c.457C>T) pathogenic?

PHKG1 p.Pro153Ser (c.457C>T) is classified Uncertain significance in PHKG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-14). AlphaMissense: likely pathogenic (0.9763); Very rare (popmax 0.00133%, afr).

How common is PHKG1 p.Pro153Ser (c.457C>T) in the general population?

PHKG1 p.Pro153Ser (c.457C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about PHKG1 p.Pro153Ser (c.457C>T)?

AlphaMissense predicts likely pathogenic (score 0.9763) — an in-silico prediction, not a clinical call.

PHKG1 p.Pro153Ser

c.457C>T · rs539584077 · VCV2267243

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9763 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9763	likely pathogenic
REVEL	0.697	pathogenic-leaning
SaProt	LLR -13.12	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 7,884 bp · p 0.15 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00133% African / African-American · 1/75,048 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000372% 6/1,614,130 alleles · very rare exomes 5/1,461,842 · genomes 1/152,288 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,048
European (non-Finnish)	0.000424%	236,003

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: PHKG1
Protein: p.Pro153Ser
Coding: c.457C>T
MANE Select: NM_006213
dbSNP: rs539584077
Type: single nucleotide variant
Location: chr7:56083368 (GRCh38)
Gene constraint: LOEUF 1.314 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.11 · 10 PDB
Residue 153: the protein kinase domain; an α-helix

Full PHKG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PHKG1 p.Ala279Val Uncertain significance ★ ⚠ same type
PHKG1 p.Ala282Gly Uncertain significance ★ ⚠ same type
PHKG1 p.Arg132Gln Uncertain significance ★ ⚠ same type
PHKG1 p.Arg182Gln Uncertain significance ★ ⚠ same type
PHKG1 p.Arg233Trp Uncertain significance ★ ⚠ same type
PHKG1 p.Arg297Gln Uncertain significance ★ ⚠ same type
PHKG1 p.Arg297Trp Uncertain significance ★ ⚠ same type
PHKG1 p.Arg302Gln 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/phkg1-p-pro153ser (accessed [today's date]).

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