Is PHKA2 p.Ala65Ser (c.193G>T) pathogenic?

PHKA2 p.Ala65Ser (c.193G>T) is classified Uncertain significance in PHKA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-20). AlphaMissense: likely benign (0.2408); Absent from gnomAD v4.1.

How common is PHKA2 p.Ala65Ser (c.193G>T) in the general population?

PHKA2 p.Ala65Ser (c.193G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PHKA2 p.Ala65Ser (c.193G>T)?

AlphaMissense predicts likely benign (score 0.2408) — an in-silico prediction, not a clinical call.

PHKA2 p.Ala65Ser

c.193G>T · rs2147995123 · VCV1698179

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2408 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2408	likely benign
REVEL	0.821	moderately pathogenic-leaning
SaProt	LLR -6.34	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 7.5	GERP 1.9, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 45 kb · p 5e-08 · 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PHKA2
Protein: p.Ala65Ser
Coding: c.193G>T
MANE Select: NM_000292
dbSNP: rs2147995123
Type: single nucleotide variant
Location: chrX:18954298 (GRCh38)
Structure: AlphaFold pLDDT 81.36

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

Similar variants

PHKA2 c.1325-2A>G Likely pathogenic ★★ same type
PHKA2 c.2597+1G>A Pathogenic/Likely pathogenic ★★ same type
PHKA2 c.537+2T>C Pathogenic/Likely pathogenic ★★ same type
PHKA2 c.918+1G>A Pathogenic/Likely pathogenic ★★ same type
PHKA2 p.Arg1111Ter Pathogenic ★★ same type
PHKA2 p.Arg186Cys Pathogenic/Likely pathogenic ★★ same type
PHKA2 p.Arg186His Likely pathogenic ★★ same type
PHKA2 p.Arg295Cys Pathogenic/Likely pathogenic ★★ 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/phka2-p-ala65ser (accessed [today's date]).

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