Is PHKA2 p.Pro315Arg (c.944C>G) pathogenic?

PHKA2 p.Pro315Arg (c.944C>G) is classified Likely benign in PHKA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-23). AlphaMissense: likely benign (0.3362); Ultra-rare (popmax 0.0237%, eas); Associated with Inborn genetic diseases.

What condition is associated with PHKA2 p.Pro315Arg (c.944C>G)?

PHKA2 p.Pro315Arg (c.944C>G) is associated with Inborn genetic diseases (ClinVar).

How common is PHKA2 p.Pro315Arg (c.944C>G) in the general population?

PHKA2 p.Pro315Arg (c.944C>G) is ultra-rare (popmax 0.0237%, eas) (gnomAD).

What do computational predictors say about PHKA2 p.Pro315Arg (c.944C>G)?

AlphaMissense predicts likely benign (score 0.3362) — an in-silico prediction, not a clinical call.

PHKA2 p.Pro315Arg

c.944C>G · rs773008663 · VCV2606252

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3362 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0237%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3362	likely benign
REVEL	0.553	indeterminate
SaProt	LLR -13.50	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 45 kb · p 5e-08 · regional, not allelic
Overall
CADD	22.8	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

Grpmax group 0.0237% East Asian · 8/33,824 alleles

Filtering AF 0.0117% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0085%

Overall 0.000995% 12/1,206,516 alleles · ultra-rare exomes 12/1,092,593 · genomes 0/113,923 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0237%	4,228
Remaining individualsnot grpmax-eligible	0.00422%	23,723
South Asian	0.00352%	28,439

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.Pro315Arg
Coding: c.944C>G
MANE Select: NM_000292
dbSNP: rs773008663
Type: single nucleotide variant
Location: chrX:18938724 (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-pro315arg (accessed [today's date]).

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