Is PHKA2 p.Phe141fs (c.420_421del) pathogenic?

PHKA2 p.Phe141fs (c.420421del) is classified Pathogenic in PHKA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-03). Associated with PHKA2-related disorder.

What condition is associated with PHKA2 p.Phe141fs (c.420_421del)?

PHKA2 p.Phe141fs (c.420_421del) is associated with PHKA2-related disorder (ClinVar).

PHKA2 p.Phe141fs

c.420_421del · VCV4949161

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

PHKA2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 33
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.2	GERP -0.49, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: PHKA2
Protein: p.Phe141fs
Coding: c.420_421del
MANE Select: NM_000292
Type: Microsatellite
Location: chrX:18951137 (GRCh38)
Structure: AlphaFold pLDDT 81.36
Residue 141: a UniProt-annotated variant site (in gsd9a; type 1)

Full PHKA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PHKA2-related disorder

Similar variants

PHKA2 p.Leu1188fs Likely pathogenic ★ same condition
PHKA2 p.Phe141del Pathogenic same residue
PHKA2 p.Arg295Cys Pathogenic/Likely pathogenic ★★ same condition
PHKA2 p.Arg45Gln Pathogenic/Likely pathogenic ★★ same condition
PHKA2 p.Glu1112Ter Pathogenic ★★ same condition
PHKA2 p.Cys553Arg Uncertain significance ★★ ⚠ same condition
PHKA2 p.Asp127fs Likely pathogenic ★ same condition
PHKA2 p.Glu1142fs Likely pathogenic ★ 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/phka2-p-phe141fs (accessed [today's date]).

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