Is PHEX p.Ser568Pro (c.1702T>C) pathogenic?

PHEX p.Ser568Pro (c.1702T>C) is classified Uncertain significance in PHEX (ClinVar, Single submitter, 1 submitter; last evaluated 2019-10-21). AlphaMissense: likely pathogenic (0.7219); No allele count reported in gnomAD v4.1 (AN 1,152,473).

How common is PHEX p.Ser568Pro (c.1702T>C) in the general population?

PHEX p.Ser568Pro (c.1702T>C) is no allele count reported in gnomAD v4.1 (AN 1,152,473) (gnomAD).

What do computational predictors say about PHEX p.Ser568Pro (c.1702T>C)?

AlphaMissense predicts likely pathogenic (score 0.7219) — an in-silico prediction, not a clinical call.

PHEX p.Ser568Pro

c.1702T>C · rs768470624 · VCV954162

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7219 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,152,473)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7219	likely pathogenic
REVEL	0.881	moderately pathogenic-leaning
SaProt	LLR -10.76	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.31	acceptor loss · deltas
Pangolin	Δ0.28	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.9	GERP 2.5, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 215 kb · p 6.8e-05 · regional, not allelic
Overall
CADD	26.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,152,473). 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.Ser568Pro
Coding: c.1702T>C
MANE Select: NM_000444
dbSNP: rs768470624
Type: single nucleotide variant
Location: chrX:22219037 (GRCh38)
Structure: AlphaFold pLDDT 94.58
Residue 568: the peptidase m13 domain

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

Similar variants

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
PHEX c.1173+2T>C Pathogenic ★★ same type
PHEX c.1173+5G>C 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-ser568pro (accessed [today's date]).

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