Is HAL p.Val80Met (c.238G>A) pathogenic?

HAL p.Val80Met (c.238G>A) is classified Uncertain significance in HAL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-22). AlphaMissense: likely pathogenic (0.5957); Ultra-rare (popmax 0.0505%, sas).

How common is HAL p.Val80Met (c.238G>A) in the general population?

HAL p.Val80Met (c.238G>A) is ultra-rare (popmax 0.0505%, sas) (gnomAD).

What do computational predictors say about HAL p.Val80Met (c.238G>A)?

AlphaMissense predicts likely pathogenic (score 0.5957) — an in-silico prediction, not a clinical call.

HAL p.Val80Met

c.238G>A · VCV4674856

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5957 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0505%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.5957	likely pathogenic
REVEL	0.525	indeterminate
SaProt	LLR -9.43	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 0.77, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 22 kb · p 0.18 · regional, not allelic
Overall
CADD	27.3	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 0.0505% South Asian · 46/91,090 alleles

Filtering AF 0.0389% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0348%

Overall 0.00496% 80/1,613,436 alleles · ultra-rare exomes 72/1,461,074 · genomes 8/152,362 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0505%	1,980
Admixed American	0.0117%	8,576
African / African-American	0.00666%	15,014
Remaining individualsnot grpmax-eligible	0.0064%	15,626
European (non-Finnish)	0.00153%	65,557

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.Val80Met
Coding: c.238G>A
MANE Select: NM_002108
Type: single nucleotide variant
Location: chr12:95995673 (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-val80met (accessed [today's date]).

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