Is HAL p.Asn307= (c.921T>C) pathogenic?

HAL p.Asn307= (c.921T>C) is classified Benign in HAL (ClinVar, Multiple submitters, 3 submitters; last evaluated 2018-01-12). Common (popmax 18.8%, afr) — too common for a highly-penetrant pathogenic allele; Associated with histidinemia.

What condition is associated with HAL p.Asn307= (c.921T>C)?

HAL p.Asn307= (c.921T>C) is associated with histidinemia (ClinVar).

How is Histidinemia inherited?

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

HAL p.Asn307=

Q: How common is HAL p.Asn307= (c.921T>C) in the general population?

HAL p.Asn307= (c.921T>C) is common (popmax 18.8%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.921T>C · rs11108364 · VCV310712

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 18.8%, 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 -9.7	GERP -3.1
Overall
CADD	0.027	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 18.8% African / African-American · 14,094/74,946 alleles

Filtering AF 18.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 18.4%

Overall 6.09% 98,335/1,613,544 alleles · common exomes 84,178/1,461,344 · genomes 14,157/152,200 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	18.8%	5
Middle Eastern	13.9%	7
East Asian	10.1%	10
Ashkenazi Jewishnot grpmax-eligible	9.56%	10
Remaining individualsnot grpmax-eligible	6.85%	15
South Asian	5.49%	18
European (non-Finnish)	5.24%	19
Amishnot grpmax-eligible	5.04%	20
Admixed American	5.01%	20
Finnishnot grpmax-eligible	2.89%	35

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.Asn307=
Coding: c.921T>C
MANE Select: NM_002108
dbSNP: rs11108364
Type: single nucleotide variant
Location: chr12:95987197 (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-asn307 (accessed [today's date]).

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