Is HELLS p.Lys110Arg (c.329A>G) pathogenic?

HELLS p.Lys110Arg (c.329A>G) is classified Uncertain significance in HELLS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-05). AlphaMissense: likely benign (0.0682); Very rare (popmax 8.6e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with HELLS p.Lys110Arg (c.329A>G)?

HELLS p.Lys110Arg (c.329A>G) is associated with Inborn genetic diseases (ClinVar).

How common is HELLS p.Lys110Arg (c.329A>G) in the general population?

HELLS p.Lys110Arg (c.329A>G) is very rare (popmax 8.6e-05%, nfe) (gnomAD).

What do computational predictors say about HELLS p.Lys110Arg (c.329A>G)?

AlphaMissense predicts likely benign (score 0.0682) — an in-silico prediction, not a clinical call.

HELLS p.Lys110Arg

c.329A>G · rs1452977946 · VCV1474369

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0682 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.6e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0682	likely benign
REVEL	0.052	moderately benign-leaning
SaProt	LLR -7.58	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.007	GERP -0.35
Regional constraint	o/e 0.94	unconstrained · MANE · 16 kb · p 0.48 · regional, not allelic
Overall
CADD	13.13	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 8.6e-05% European (non-Finnish) · 1/1,163,064 alleles

Overall 6.39e-05% 1/1,565,056 alleles · very rare exomes 0/1,412,822 · genomes 1/152,234 · 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: HELLS
Protein: p.Lys110Arg
Coding: c.329A>G
MANE Select: NM_018063
dbSNP: rs1452977946
Type: single nucleotide variant
Location: chr10:94558191 (GRCh38)
Gene constraint: LOEUF 0.587 · pLI 0.63 (gnomAD)
Structure: AlphaFold pLDDT 68.76 · 4 PDB
Residue 110: the 'disordered' region

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.Lys110Glu Uncertain significance ★ ⚠ same residue
HELLS p.Ala16Pro Uncertain significance ★★ ⚠ same condition
HELLS p.Arg319Trp Uncertain significance ★★ ⚠ same condition
HELLS p.Arg507Gln 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

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-lys110arg (accessed [today's date]).

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