Is HAL p.Ile600= (c.1800C>T) pathogenic?

HAL p.Ile600= (c.1800C>T) is classified Likely benign in HAL (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-24). Ultra-rare (popmax 0.0176%, sas); Associated with HAL-related disorder.

What condition is associated with HAL p.Ile600= (c.1800C>T)?

HAL p.Ile600= (c.1800C>T) is associated with HAL-related disorder (ClinVar).

How common is HAL p.Ile600= (c.1800C>T) in the general population?

HAL p.Ile600= (c.1800C>T) is ultra-rare (popmax 0.0176%, sas) (gnomAD).

HAL p.Ile600=

c.1800C>T · rs137860207 · VCV3042715

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0176%, sas)

Conditions

HAL-related disorder

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 -4.5	GERP -3.1
Overall
CADD	2.216	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0176% South Asian · 16/91,074 alleles

Filtering AF 0.011% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00888%

Overall 0.00186% 30/1,613,914 alleles · ultra-rare exomes 26/1,461,730 · genomes 4/152,184 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0176%	5,692
Admixed American	0.00667%	15,002
African / African-American	0.004%	24,976
Remaining individualsnot grpmax-eligible	0.0016%	62,480
European (non-Finnish)	0.000509%	196,654

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.Ile600=
Coding: c.1800C>T
MANE Select: NM_002108
dbSNP: rs137860207
Type: single nucleotide variant
Location: chr12:95976462 (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

HAL-related disorder

Similar variants

HAL p.Ile600Val Uncertain significance ★ ⚠ same residue
HAL c.248-5T>C Likely benign same condition
HAL p.Ala526= Likely benign same condition
HAL p.Pro652= Likely benign same condition
HAL p.Pro95= Likely benign same condition
HAL c.*392C>T Uncertain significance ★★ same type
HAL p.Arg9Cys Uncertain significance ★★ ⚠ same type
HAL p.Asn476Lys Uncertain significance ★★ ⚠ same type

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-ile600 (accessed [today's date]).

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