Is PHEX p.Arg82Gln (c.245G>A) pathogenic?

PHEX p.Arg82Gln (c.245G>A) is classified Benign in PHEX (ClinVar, Single submitter, 2 submitters; last evaluated 2021-12-23). AlphaMissense: likely benign (0.0692); Ultra-rare (popmax 0.051%, sas).

How common is PHEX p.Arg82Gln (c.245G>A) in the general population?

PHEX p.Arg82Gln (c.245G>A) is ultra-rare (popmax 0.051%, sas) (gnomAD).

What do computational predictors say about PHEX p.Arg82Gln (c.245G>A)?

AlphaMissense predicts likely benign (score 0.0692) — an in-silico prediction, not a clinical call.

PHEX p.Arg82Gln

c.245G>A · rs769541316 · VCV2068395

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0692 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.051%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0692	likely benign
REVEL	0.104	moderately benign-leaning
SaProt	LLR -4.58	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.50	acceptor gain · deltas
Pangolin	Δ0.21	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 3.7	GERP 1.4, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 215 kb · p 6.8e-05 · regional, not allelic
Overall
CADD	21.7	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 0.051% South Asian · 29/56,868 alleles

Filtering AF 0.0364% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0316%

Overall 0.0029% 35/1,206,750 alleles · ultra-rare exomes 35/1,093,440 · genomes 0/113,310 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.051%	1,961
Middle Eastern	0.0461%	2,172
Admixed American	0.00435%	22,973
Remaining individualsnot grpmax-eligible	0.00421%	23,749

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.Arg82Gln
Coding: c.245G>A
MANE Select: NM_000444
dbSNP: rs769541316
Type: single nucleotide variant
Location: chrX:22047107 (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

Similar variants

PHEX p.Arg82Leu Uncertain significance ★ ⚠ same residue
PHEX p.Arg82Trp Conflicting classifications of pathogenicity ★ ⚠ 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-arg82gln (accessed [today's date]).

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