Is HELLS p.Asp522Val (c.1565A>T) pathogenic?

HELLS p.Asp522Val (c.1565A>T) is classified Uncertain significance in HELLS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-09). AlphaMissense: likely benign (0.1013); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with HELLS p.Asp522Val (c.1565A>T)?

HELLS p.Asp522Val (c.1565A>T) is associated with Inborn genetic diseases (ClinVar).

How common is HELLS p.Asp522Val (c.1565A>T) in the general population?

HELLS p.Asp522Val (c.1565A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about HELLS p.Asp522Val (c.1565A>T)?

AlphaMissense predicts likely benign (score 0.1013) — an in-silico prediction, not a clinical call.

HELLS p.Asp522Val

c.1565A>T · rs2493270056 · VCV3105074

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1013 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1013	likely benign
REVEL	0.652	pathogenic-leaning
SaProt	LLR -7.70	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>G here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.2	GERP 0.55, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 5,267 bp · p 2e-05 · regional, not allelic
Overall
CADD	23.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: HELLS
Protein: p.Asp522Val
Coding: c.1565A>T
MANE Select: NM_018063
dbSNP: rs2493270056
Type: single nucleotide variant
Location: chr10:94590489 (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.Asp522Gly 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-asp522val (accessed [today's date]).

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