Is HAL p.Tyr164= (c.492C>T) pathogenic?

HAL p.Tyr164= (c.492C>T) is classified Benign/Likely benign in HAL (ClinVar, Multiple submitters, 3 submitters; last evaluated 2019-01-08). Low-frequency (popmax 3.62%, afr); Associated with histidinemia.

What condition is associated with HAL p.Tyr164= (c.492C>T)?

HAL p.Tyr164= (c.492C>T) is associated with histidinemia (ClinVar).

How common is HAL p.Tyr164= (c.492C>T) in the general population?

HAL p.Tyr164= (c.492C>T) is low-frequency (popmax 3.62%, afr) (gnomAD).

How is Histidinemia inherited?

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

HAL p.Tyr164=

c.492C>T · rs17024973 · VCV773028

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.62%, afr)

Conditions

histidinemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.32 · evaluated, not missing
Constraint at this position
Conservation	phyloP -6.9	GERP -3.1
Overall
CADD	8.294	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.62% African / African-American · 2,676/73,880 alleles

Filtering AF 3.51% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.46%

Overall 0.19% 2,973/1,563,514 alleles · low-frequency exomes 1,395/1,411,240 · genomes 1,578/152,274 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.62%	28
Remaining individualsnot grpmax-eligible	0.179%	557
Admixed American	0.17%	588
Middle Eastern	0.0503%	1,989
South Asian	0.00889%	11,253
European (non-Finnish)	0.00644%	15,535
East Asian	0.00224%	44,650
Finnishnot grpmax-eligible	0.00156%	63,974

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.Tyr164=
Coding: c.492C>T
MANE Select: NM_002108
dbSNP: rs17024973
Type: single nucleotide variant
Location: chr12:95993831 (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-tyr164 (accessed [today's date]).

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