Is PHEX p.Ala22Phe (c.64_65delinsTT) pathogenic?

PHEX p.Ala22Phe (c.6465delinsTT) is classified Uncertain significance in PHEX (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-28). No gnomAD frequency available for this variant.

How common is PHEX p.Ala22Phe (c.64_65delinsTT) in the general population?

PHEX p.Ala22Phe (c.64_65delinsTT) is no gnomAD frequency available for this variant (gnomAD).

PHEX p.Ala22Phe

c.64_65delinsTT · rs2146974307 · VCV1331209

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 0.88, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 215 kb · p 6.8e-05 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PHEX
Protein: p.Ala22Phe
Coding: c.64_65delinsTT
MANE Select: NM_000444
dbSNP: rs2146974307
Type: Indel
Location: chrX:22033069 (GRCh38)
Structure: AlphaFold pLDDT 94.58

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

Similar variants

PHEX p.Ala22Ser Likely benign ★ same residue
PHEX c.289_349+836delinsAAGATATGCCT Likely pathogenic ★ same type
PHEX c.934-3_934-1delinsTCA Pathogenic ★ same type
PHEX p.Ala62Lys Likely pathogenic ★ same type
PHEX p.Met1fs Pathogenic ★ same type
PHEX p.Phe654fs Pathogenic ★ same type
PHEX p.Ser379_Arg380delinsArgTrp Pathogenic ★ same type
PHEX p.Ser722fs 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/phex-p-ala22phe (accessed [today's date]).

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