Is HAL p.Ala503Thr (c.1507G>A) pathogenic?

HAL p.Ala503Thr (c.1507G>A) is classified Uncertain significance in HAL (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-26). AlphaMissense: ambiguous (0.4701); Very rare (popmax 8.47e-05%, nfe).

How common is HAL p.Ala503Thr (c.1507G>A) in the general population?

HAL p.Ala503Thr (c.1507G>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about HAL p.Ala503Thr (c.1507G>A)?

AlphaMissense predicts ambiguous (score 0.4701) — an in-silico prediction, not a clinical call.

HAL p.Ala503Thr

c.1507G>A · rs2499639167 · VCV2257458

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4701 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4701	ambiguous
REVEL	0.755	pathogenic-leaning
SaProt	LLR -11.92	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 22 kb · p 0.18 · regional, not allelic
Overall
CADD	27.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,964 alleles

Overall 6.2e-05% 1/1,613,510 alleles · very rare exomes 1/1,461,262 · genomes 0/152,248 · joint denominator

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.Ala503Thr
Coding: c.1507G>A
MANE Select: NM_002108
dbSNP: rs2499639167
Type: single nucleotide variant
Location: chr12:95980568 (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

Similar variants

HAL c.*392C>T Uncertain significance ★★ same type
HAL p.Arg9Cys Uncertain significance ★★ ⚠ same type
HAL p.Asn476Lys Uncertain significance ★★ ⚠ same type
HAL p.Glu472Lys Uncertain significance ★★ ⚠ same type
HAL p.Gly165Ser Uncertain significance ★★ ⚠ same type
HAL p.Ile458Thr Uncertain significance ★★ ⚠ same type
HAL p.Leu242Met Uncertain significance ★★ ⚠ same type
HAL p.Phe485Leu 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-ala503thr (accessed [today's date]).

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