Is HELLS p.Leu275= (c.825T>A) pathogenic?

HELLS p.Leu275= (c.825T>A) is classified Likely benign in HELLS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-11). Absent from gnomAD v4.1.

How common is HELLS p.Leu275= (c.825T>A) in the general population?

HELLS p.Leu275= (c.825T>A) is absent from gnomAD v4.1 (gnomAD).

HELLS p.Leu275=

c.825T>A · rs2493175686 · VCV2974944

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.049	GERP -4.5, phastCons 0.96
Overall
CADD	6.475	PHRED · no single calibrated threshold — expert panels disagree

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.Leu275=
Coding: c.825T>A
MANE Select: NM_018063
dbSNP: rs2493175686
Type: single nucleotide variant
Location: chr10:94574673 (GRCh38)
Gene constraint: LOEUF 0.587 · pLI 0.63 (gnomAD)
Structure: AlphaFold pLDDT 68.76 · 4 PDB
Residue 275: the helicase atp-binding domain

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

Similar variants

HELLS c.370+2T>A Pathogenic ★★ same type
HELLS c.1488+4T>C Uncertain significance ★★ same type
HELLS p.Ala16Pro Uncertain significance ★★ ⚠ same type
HELLS p.Arg319Trp Uncertain significance ★★ ⚠ same type
HELLS p.Arg507Gln Uncertain significance ★★ ⚠ same type
HELLS p.Arg513Gly Uncertain significance ★★ ⚠ same type
HELLS p.Arg541Gln Uncertain significance ★★ ⚠ same type
HELLS p.Arg5Trp Uncertain significance ★★ ⚠ 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/hells-p-leu275 (accessed [today's date]).

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