Is PHKA2 p.Asp127= (c.381C>T) pathogenic?

PHKA2 p.Asp127= (c.381C>T) is classified Likely benign in PHKA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-11). Ultra-rare (popmax 0.0231%, mid); Associated with Inborn genetic diseases.

What condition is associated with PHKA2 p.Asp127= (c.381C>T)?

PHKA2 p.Asp127= (c.381C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PHKA2 p.Asp127= (c.381C>T) in the general population?

PHKA2 p.Asp127= (c.381C>T) is ultra-rare (popmax 0.0231%, mid) (gnomAD).

PHKA2 p.Asp127=

c.381C>T · VCV4627406

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0231%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.3	GERP -3.8
Overall
CADD	2.065	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0231% Middle Eastern · 1/4,328 alleles

Filtering AF 0.000811% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000625%

Overall 0.00124% 15/1,209,589 alleles · ultra-rare exomes 13/1,097,451 · genomes 2/112,138 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0231%	4,328
Remaining individualsnot grpmax-eligible	0.0021%	47,593
European (non-Finnish)	0.00145%	68,817

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.Asp127=
Coding: c.381C>T
MANE Select: NM_000292
Type: single nucleotide variant
Location: chrX:18951177 (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.Asp127Asn Uncertain significance ★ ⚠ same residue
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

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-asp127 (accessed [today's date]).

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