Is PHEX p.Arg82Trp (c.244C>T) pathogenic?

PHEX p.Arg82Trp (c.244C>T) is classified Conflicting classifications of pathogenicity in PHEX (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-02-27). AlphaMissense: likely benign (0.1961); Very rare (popmax 0.00657%, amr); Associated with Inborn genetic diseases.

What condition is associated with PHEX p.Arg82Trp (c.244C>T)?

PHEX p.Arg82Trp (c.244C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PHEX p.Arg82Trp (c.244C>T) in the general population?

PHEX p.Arg82Trp (c.244C>T) is very rare (popmax 0.00657%, amr) (gnomAD).

What do computational predictors say about PHEX p.Arg82Trp (c.244C>T)?

AlphaMissense predicts likely benign (score 0.1961) — an in-silico prediction, not a clinical call.

PHEX p.Arg82Trp

c.244C>T · rs1365010493 · VCV2673219

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1961 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00657%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1961	likely benign
REVEL	0.506	indeterminate
SaProt	LLR -11.02	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.82 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.9	GERP 1.4, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 215 kb · p 6.8e-05 · regional, not allelic
Overall
CADD	27.5	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 0.00657% Admixed American · 3/45,668 alleles

Filtering AF 0.00174% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000883%

Overall 0.00149% 18/1,205,065 alleles · very rare exomes 16/1,093,285 · genomes 2/111,780 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00657%	15,223
Remaining individualsnot grpmax-eligible	0.00422%	23,713
African / African-American	0.0035%	28,535
East Asian	0.00296%	33,761
South Asian	0.00176%	56,718
European (non-Finnish)	0.00101%	98,984

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.Arg82Trp
Coding: c.244C>T
MANE Select: NM_000444
dbSNP: rs1365010493
Type: single nucleotide variant
Location: chrX:22047106 (GRCh38)
Structure: AlphaFold pLDDT 94.58
Residue 82: the peptidase m13 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PHEX p.Arg82Leu Uncertain significance ★ ⚠ same residue
PHEX p.Arg82Gln Benign ★ same residue
PHEX p.Ala524Val Uncertain significance ★★ ⚠ same condition
PHEX p.Arg166His Uncertain significance ★★ ⚠ same condition
PHEX p.Arg443His Uncertain significance ★★ ⚠ same condition
PHEX p.Arg651Trp Uncertain significance ★★ ⚠ same condition
PHEX p.Arg697Lys Uncertain significance ★★ same condition
PHEX p.Asn680Lys Uncertain significance ★★ ⚠ same condition

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-arg82trp (accessed [today's date]).

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