Is HELLS p.Thr714Arg (c.2141C>G) pathogenic?

HELLS p.Thr714Arg (c.2141C>G) is classified Uncertain significance in HELLS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-15). AlphaMissense: likely benign (0.1334); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with HELLS p.Thr714Arg (c.2141C>G)?

HELLS p.Thr714Arg (c.2141C>G) is associated with Inborn genetic diseases (ClinVar).

How common is HELLS p.Thr714Arg (c.2141C>G) in the general population?

HELLS p.Thr714Arg (c.2141C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about HELLS p.Thr714Arg (c.2141C>G)?

AlphaMissense predicts likely benign (score 0.1334) — an in-silico prediction, not a clinical call.

HELLS p.Thr714Arg

c.2141C>G · VCV4269940

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1334 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1334	likely benign
REVEL	0.616	indeterminate
SaProt	LLR -8.43	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 0.99, phastCons 1
Regional constraint	o/e 0.28	constrained · MANE · 1,268 bp · p 2.1e-10 · regional, not allelic
Overall
CADD	27.6	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

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.Thr714Arg
Coding: c.2141C>G
MANE Select: NM_018063
Type: single nucleotide variant
Location: chr10:94594747 (GRCh38)
Gene constraint: LOEUF 0.587 · pLI 0.63 (gnomAD)
Structure: AlphaFold pLDDT 68.76 · 4 PDB
Residue 714: the helicase c-terminal domain

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.Thr714= Likely benign ★ 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-thr714arg (accessed [today's date]).

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