Is HAL p.Glu11= (c.33A>G) pathogenic?

HAL p.Glu11= (c.33A>G) is classified Uncertain significance in HAL (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Low-frequency (popmax 1.15%, eas); Associated with histidinemia.

What condition is associated with HAL p.Glu11= (c.33A>G)?

HAL p.Glu11= (c.33A>G) is associated with histidinemia (ClinVar).

How common is HAL p.Glu11= (c.33A>G) in the general population?

HAL p.Glu11= (c.33A>G) is low-frequency (popmax 1.15%, eas) (gnomAD).

How is Histidinemia inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

HAL p.Glu11=

c.33A>G · rs118129111 · VCV883085

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 1.15%, eas)

Conditions

histidinemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.6	GERP -3.4
Overall
CADD	1.38	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.15% East Asian · 514/44,876 alleles

Filtering AF 1.06% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.03%

Overall 0.0347% 557/1,607,056 alleles · low-frequency exomes 523/1,454,760 · genomes 34/152,296 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	1.15%	87
South Asian	0.0296%	3,373
Remaining individualsnot grpmax-eligible	0.0192%	5,205
European (non-Finnish)	0.000339%	294,970

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: HAL
Protein: p.Glu11=
Coding: c.33A>G
MANE Select: NM_002108
dbSNP: rs118129111
Type: single nucleotide variant
Location: chr12:95995878 (GRCh38)
Gene constraint: LOEUF 1.213 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.83

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

Disease context

histidinemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Histidinemia (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Sweden)

Similar variants

HAL c.*392C>T Uncertain significance ★★ same condition
HAL p.Arg9Cys Uncertain significance ★★ ⚠ same condition
HAL p.Asn476Lys Uncertain significance ★★ ⚠ same condition
HAL p.Glu472Lys Uncertain significance ★★ ⚠ same condition
HAL p.Gly165Ser Uncertain significance ★★ ⚠ same condition
HAL p.Leu242Met Uncertain significance ★★ ⚠ same condition
HAL p.Phe485Leu Uncertain significance ★★ ⚠ same condition
HAL p.Thr123Met 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/hal-p-glu11 (accessed [today's date]).

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