Is HAL c.855+9C>T pathogenic?

HAL c.855+9C>T is classified Conflicting classifications of pathogenicity in HAL (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-11-14). Rare (popmax 0.911%, afr); Associated with histidinemia.

What condition is associated with HAL c.855+9C>T?

HAL c.855+9C>T is associated with histidinemia (ClinVar).

How common is HAL c.855+9C>T in the general population?

HAL c.855+9C>T is rare (popmax 0.911%, afr) (gnomAD).

How is Histidinemia inherited?

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

HAL c.855+9C>T

rs35144639 · VCV310714

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.911%, afr)

Conditions

histidinemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +9	near-intronic (+9 nt from the splice site)
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.4	GERP -2.8, phastCons 0.001
Non-coding constraint	Z 0.87	1 kb window · o/e 0.90 · regional · uncalibrated
Overall
CADD	2.442	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.911% African / African-American · 683/74,976 alleles

Filtering AF 0.854% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.832%

Overall 0.163% 2,623/1,610,460 alleles · rare exomes 2,133/1,458,138 · genomes 490/152,322 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.911%	110
Remaining individualsnot grpmax-eligible	0.216%	462
Admixed American	0.15%	667
European (non-Finnish)	0.145%	689
Middle Eastern	0.0825%	1,212
South Asian	0.0022%	45,506

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.855+9C>T
MANE Select: NM_002108
dbSNP: rs35144639
Type: single nucleotide variant
Location: chr12:95990384 (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-855-plus-9c-t (accessed [today's date]).

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