Is HELLS p.Gly11Arg (c.31G>C) pathogenic?

HELLS p.Gly11Arg (c.31G>C) is classified Uncertain significance in HELLS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-24). AlphaMissense: likely benign (0.1312); Very rare (popmax 0.00584%, amr).

How common is HELLS p.Gly11Arg (c.31G>C) in the general population?

HELLS p.Gly11Arg (c.31G>C) is very rare (popmax 0.00584%, amr) (gnomAD).

What do computational predictors say about HELLS p.Gly11Arg (c.31G>C)?

AlphaMissense predicts likely benign (score 0.1312) — an in-silico prediction, not a clinical call.

HELLS p.Gly11Arg

c.31G>C · rs1043925031 · VCV1371458

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1312 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00584%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1312	likely benign
REVEL	0.463	indeterminate
SaProt	LLR -7.23	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.37	donor loss · deltas
Pangolin	Δ0.47	loss · gain 0.15 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 5.1	GERP 0.075, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 8,258 bp · p 0.71 · regional, not allelic
Overall
CADD	31.0	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 0.00584% Admixed American · 3/51,412 alleles

Filtering AF 0.00155% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000829%

Overall 0.000257% 4/1,556,054 alleles · very rare exomes 1/1,403,858 · genomes 3/152,196 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00584%	17,137
Remaining individualsnot grpmax-eligible	0.00166%	60,276

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.Gly11Arg
Coding: c.31G>C
MANE Select: NM_018063
dbSNP: rs1043925031
Type: single nucleotide variant
Location: chr10:94545952 (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

Similar variants

HELLS p.Gly11Cys Uncertain significance ★ ⚠ same residue
HELLS p.Gly11= Likely benign ★ same residue
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

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-gly11arg (accessed [today's date]).

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