Is HELLS p.Arg507Gln (c.1520G>A) pathogenic?

HELLS p.Arg507Gln (c.1520G>A) is classified Uncertain significance in HELLS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-12-22). AlphaMissense: likely benign (0.3106); Very rare (popmax 0.00685%, amr); Associated with Inborn genetic diseases.

What condition is associated with HELLS p.Arg507Gln (c.1520G>A)?

HELLS p.Arg507Gln (c.1520G>A) is associated with Inborn genetic diseases (ClinVar).

How common is HELLS p.Arg507Gln (c.1520G>A) in the general population?

HELLS p.Arg507Gln (c.1520G>A) is very rare (popmax 0.00685%, amr) (gnomAD).

What do computational predictors say about HELLS p.Arg507Gln (c.1520G>A)?

AlphaMissense predicts likely benign (score 0.3106) — an in-silico prediction, not a clinical call.

HELLS p.Arg507Gln

c.1520G>A · rs368865793 · VCV1445692

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3106 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00685%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3106	likely benign
REVEL	0.665	pathogenic-leaning
SaProt	LLR -10.44	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 5,267 bp · p 2e-05 · regional, not allelic
Overall
CADD	33.0	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 0.00685% Admixed American · 4/58,358 alleles

Filtering AF 0.0023% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00138%

Overall 0.000746% 12/1,608,976 alleles · very rare exomes 6/1,456,914 · genomes 6/152,062 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00685%	14,590
Remaining individualsnot grpmax-eligible	0.00161%	62,304
Finnishnot grpmax-eligible	0.00156%	63,992
European (non-Finnish)	0.000509%	196,509

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: HELLS
Protein: p.Arg507Gln
Coding: c.1520G>A
MANE Select: NM_018063
dbSNP: rs368865793
Type: single nucleotide variant
Location: chr10:94590444 (GRCh38)
Gene constraint: LOEUF 0.587 · pLI 0.63 (gnomAD)
Structure: AlphaFold pLDDT 68.76 · 4 PDB

Full HELLS 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

HELLS p.Arg507Ter Pathogenic ★ same residue
HELLS p.Ala16Pro Uncertain significance ★★ ⚠ same condition
HELLS p.Arg319Trp Uncertain significance ★★ ⚠ same condition
HELLS p.Arg541Gln Uncertain significance ★★ ⚠ same condition
HELLS p.Arg5Trp Uncertain significance ★★ ⚠ same condition
HELLS p.Arg66Cys Uncertain significance ★★ ⚠ same condition
HELLS p.Arg721Cys Uncertain significance ★★ ⚠ same condition
HELLS p.Asp117Gly 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/hells-p-arg507gln (accessed [today's date]).

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