Is PHKA2 p.Ser960Arg (c.2880T>A) pathogenic?

PHKA2 p.Ser960Arg (c.2880T>A) is classified Uncertain significance in PHKA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-30). AlphaMissense: likely pathogenic (0.9764); Very rare (popmax 0.00296%, eas); Associated with Inborn genetic diseases.

What condition is associated with PHKA2 p.Ser960Arg (c.2880T>A)?

PHKA2 p.Ser960Arg (c.2880T>A) is associated with Inborn genetic diseases (ClinVar).

How common is PHKA2 p.Ser960Arg (c.2880T>A) in the general population?

PHKA2 p.Ser960Arg (c.2880T>A) is very rare (popmax 0.00296%, eas) (gnomAD).

What do computational predictors say about PHKA2 p.Ser960Arg (c.2880T>A)?

AlphaMissense predicts likely pathogenic (score 0.9764) — an in-silico prediction, not a clinical call.

PHKA2 p.Ser960Arg

c.2880T>A · rs1227613844 · VCV2552834

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9764 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00296%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9764	likely pathogenic · top 9% in PHKA2
REVEL	0.828	moderately pathogenic-leaning
SaProt	LLR -8.65	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.3	GERP -1.8, phastCons 0.43
Regional constraint	o/e 0.90	unconstrained · MANE · 45 kb · p 0.0065 · regional, not allelic
Overall
CADD	19.46	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 0.00296% East Asian · 1/33,764 alleles

Overall 8.3e-05% 1/1,205,037 alleles · very rare exomes 0/1,092,719 · genomes 1/112,318 · 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: PHKA2
Protein: p.Ser960Arg
Coding: c.2880T>A
MANE Select: NM_000292
dbSNP: rs1227613844
Type: single nucleotide variant
Location: chrX:18905786 (GRCh38)
Structure: AlphaFold pLDDT 81.36

Full PHKA2 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

PHKA2 p.Arg86Ter Pathogenic/Likely pathogenic ★★ same condition
PHKA2 p.His132Tyr Pathogenic/Likely pathogenic ★★ same condition
PHKA2 p.Ala15Val Uncertain significance ★★ ⚠ same condition
PHKA2 p.Ala257Gly Uncertain significance ★★ ⚠ same condition
PHKA2 p.Arg154Cys Uncertain significance ★★ ⚠ same condition
PHKA2 p.Arg930Gln Uncertain significance ★★ ⚠ same condition
PHKA2 p.Arg971Cys Uncertain significance ★★ ⚠ same condition
PHKA2 p.Asp128Asn 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/phka2-p-ser960arg (accessed [today's date]).

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