Is PHEX p.Tyr207Cys (c.620A>G) pathogenic?

PHEX p.Tyr207Cys (c.620A>G) is classified Uncertain significance in PHEX (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-17). AlphaMissense: ambiguous (0.5222); Very rare (popmax 0.00217%, amr).

How common is PHEX p.Tyr207Cys (c.620A>G) in the general population?

PHEX p.Tyr207Cys (c.620A>G) is very rare (popmax 0.00217%, amr) (gnomAD).

What do computational predictors say about PHEX p.Tyr207Cys (c.620A>G)?

AlphaMissense predicts ambiguous (score 0.5222) — an in-silico prediction, not a clinical call.

PHEX p.Tyr207Cys

c.620A>G · rs763461759 · VCV2782017

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5222 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00217%, amr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5222	ambiguous
REVEL	0.797	moderately pathogenic-leaning
SaProt	LLR -11.10	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 1.5, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 215 kb · p 6.8e-05 · regional, not allelic
Overall
CADD	25.6	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00217% Admixed American · 1/45,998 alleles

Overall 8.27e-05% 1/1,209,149 alleles · very rare exomes 1/1,095,596 · genomes 0/113,553 · 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.Tyr207Cys
Coding: c.620A>G
MANE Select: NM_000444
dbSNP: rs763461759
Type: single nucleotide variant
Location: chrX:22077659 (GRCh38)
Structure: AlphaFold pLDDT 94.58
Residue 207: the peptidase m13 domain

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

Similar variants

PHEX p.Tyr207Ter Pathogenic ★★ same residue
PHEX p.Tyr207fs 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
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-tyr207cys (accessed [today's date]).

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