Is HAL c.*110C>A pathogenic?

HAL c.110C>A is classified Benign in HAL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-01-13). Common (popmax 30.1%, afr) — too common for a highly-penetrant pathogenic allele; Associated with histidinemia.

What condition is associated with HAL c.*110C>A?

HAL c.*110C>A is associated with histidinemia (ClinVar).

How is Histidinemia inherited?

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

HAL c.*110C>A

Q: How common is HAL c.*110C>A in the general population?

HAL c.*110C>A is common (popmax 30.1%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs2230885 · VCV310701

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 30.1%, afr) — too common for a highly-penetrant pathogenic allele

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 -0.22	GERP -2.4
Non-coding constraint	Z -0.10	1 kb window · o/e 1.01 · regional · uncalibrated
Overall
CADD	1.369	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 30.1% African / African-American · 18,773/62,332 alleles

Filtering AF 29.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 29.6%

Overall 18.1% 171,121/946,290 alleles · common exomes 139,788/794,158 · genomes 31,333/152,132 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	30.1%	3
Ashkenazi Jewishnot grpmax-eligible	23.3%	4
Middle Eastern	21.2%	5
European (non-Finnish)	18.9%	5
Remaining individualsnot grpmax-eligible	18.3%	5
Amishnot grpmax-eligible	16.2%	6
Finnishnot grpmax-eligible	13.4%	7
South Asian	13.3%	8
Admixed American	11.6%	9
East Asian	10.3%	10

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
Coding: c.*110C>A
MANE Select: NM_002108
dbSNP: rs2230885
Type: single nucleotide variant
Location: chr12:95974122 (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-c-star-110c-a (accessed [today's date]).

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