Is HAL p.Glu115= (c.345G>A) pathogenic?

HAL p.Glu115= (c.345G>A) is classified Likely benign in HAL (ClinVar, Single submitter, 2 submitters; last evaluated 2018-01-13). Low-frequency (popmax 1.2%, eas); Associated with histidinemia.

What condition is associated with HAL p.Glu115= (c.345G>A)?

HAL p.Glu115= (c.345G>A) is associated with histidinemia (ClinVar).

How common is HAL p.Glu115= (c.345G>A) in the general population?

HAL p.Glu115= (c.345G>A) is low-frequency (popmax 1.2%, eas) (gnomAD).

How is Histidinemia inherited?

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

HAL p.Glu115=

c.345G>A · rs188783496 · VCV881912

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.2%, eas)

Conditions

histidinemia

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 1.2	GERP -2.8, phastCons 0.63
Overall
CADD	1.806	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.2% East Asian · 539/44,862 alleles

Filtering AF 1.12% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.08%

Overall 0.0365% 588/1,610,646 alleles · low-frequency exomes 510/1,458,320 · genomes 78/152,326 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	1.2%	83
Remaining individualsnot grpmax-eligible	0.0337%	2,970
South Asian	0.0275%	3,640
African / African-American	0.00267%	37,505
European (non-Finnish)	8.5e-05%	1,176,795

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.Glu115=
Coding: c.345G>A
MANE Select: NM_002108
dbSNP: rs188783496
Type: single nucleotide variant
Location: chr12:95994156 (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-glu115 (accessed [today's date]).

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