Is PHEX p.Ser306= (c.918T>C) pathogenic?

PHEX p.Ser306= (c.918T>C) is classified Likely benign in PHEX (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-15). Ultra-rare (popmax 0.0158%, afr).

How common is PHEX p.Ser306= (c.918T>C) in the general population?

PHEX p.Ser306= (c.918T>C) is ultra-rare (popmax 0.0158%, afr) (gnomAD).

PHEX p.Ser306=

c.918T>C · VCV4694576

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0158%, afr)

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 1.2	GERP 1.7, phastCons 1
Overall
CADD	8.983	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0158% African / African-American · 9/56,795 alleles

Filtering AF 0.00823% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00617%

Overall 0.000755% 9/1,192,574 alleles · ultra-rare exomes 4/1,080,819 · genomes 5/111,755 · joint denominator

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.Ser306=
Coding: c.918T>C
MANE Select: NM_000444
Type: single nucleotide variant
Location: chrX:22097023 (GRCh38)
Structure: AlphaFold pLDDT 94.58
Residue 306: the peptidase m13 domain

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

Similar variants

PHEX p.Ser306Arg Uncertain significance ★ same residue
PHEX p.Ser306Gly Uncertain significance ★ ⚠ 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
PHEX c.1173+1G>A 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-ser306 (accessed [today's date]).

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