Is PHEX p.Pro713fs (c.2138del) pathogenic?

PHEX p.Pro713fs (c.2138del) is classified Likely pathogenic in PHEX (ClinVar, Single submitter, 1 submitter; last evaluated 2017-03-09). No allele count reported in gnomAD v4.1 (AN 1,201,206).

How common is PHEX p.Pro713fs (c.2138del) in the general population?

PHEX p.Pro713fs (c.2138del) is no allele count reported in gnomAD v4.1 (AN 1,201,206) (gnomAD).

PHEX p.Pro713fs

c.2138del · rs886041375 · VCV418408

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,201,206)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (21 of 22, 13 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.6	GERP -2.5, phastCons 0.97

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,201,206). 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.Pro713fs
Coding: c.2138del
MANE Select: NM_000444
dbSNP: rs886041375
Type: Deletion
Location: chrX:22245396 (GRCh38)
Structure: AlphaFold pLDDT 94.58
Residue 713: the peptidase m13 domain

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

Similar variants

PHEX p.Pro713His Uncertain significance ★★ ⚠ same residue
PHEX c.1079+2_1079+5del Pathogenic ★★ same type
PHEX c.187+1del Pathogenic ★★ same type
PHEX c.2147+2_2147+9del Pathogenic ★★ same type
PHEX p.Ala242fs Pathogenic ★★ same type
PHEX p.Ala295fs Pathogenic ★★ same type
PHEX p.Ala730fs Pathogenic ★★ same type
PHEX p.Asn723_Phe724insTer 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/phex-p-pro713fs (accessed [today's date]).

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