Is PHEX p.Asn647= (c.1941T>C) pathogenic?

PHEX p.Asn647= (c.1941T>C) is classified Uncertain significance in PHEX (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-07). Very rare (popmax 0.00296%, eas).

How common is PHEX p.Asn647= (c.1941T>C) in the general population?

PHEX p.Asn647= (c.1941T>C) is very rare (popmax 0.00296%, eas) (gnomAD).

PHEX p.Asn647=

c.1941T>C · VCV4949341

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00296%, eas)

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 0.3	GERP -1.2, phastCons 1
Overall
CADD	6.863	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00296% East Asian · 1/33,736 alleles

Overall 0.000166% 2/1,206,770 alleles · very rare exomes 2/1,094,991 · genomes 0/111,779 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00296%	33,736
European (non-Finnish)	0.000112%	892,188

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: PHEX
Protein: p.Asn647=
Coding: c.1941T>C
MANE Select: NM_000444
Type: single nucleotide variant
Location: chrX:22226484 (GRCh38)
Structure: AlphaFold pLDDT 94.58
Residue 647: the peptidase m13 domain

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

Similar variants

PHEX p.Asn647Ile Uncertain significance ★ ⚠ same residue
PHEX p.Asn647Ser Uncertain significance ★ ⚠ same residue
PHEX p.Asn647delinsArgTer Pathogenic ★★ same residue
PHEX c.1079+1G>A Pathogenic ★★ same type
PHEX c.1079+2T>G Pathogenic ★★ same type
PHEX c.1080-1G>A Pathogenic ★★ same type
PHEX c.1080-2A>G Pathogenic ★★ same type
PHEX c.1080-3C>G 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-asn647 (accessed [today's date]).

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