Is HAL p.Ser203Asn (c.608G>A) pathogenic?

HAL p.Ser203Asn (c.608G>A) is classified Uncertain significance in HAL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-07). AlphaMissense: likely benign (0.1354); Ultra-rare (popmax 0.0906%, afr).

How common is HAL p.Ser203Asn (c.608G>A) in the general population?

HAL p.Ser203Asn (c.608G>A) is ultra-rare (popmax 0.0906%, afr) (gnomAD).

What do computational predictors say about HAL p.Ser203Asn (c.608G>A)?

AlphaMissense predicts likely benign (score 0.1354) — an in-silico prediction, not a clinical call.

HAL p.Ser203Asn

c.608G>A · VCV4268734

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1354 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0906%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1354	likely benign
REVEL	0.239	benign-leaning
SaProt	LLR -9.01	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.63	GERP -2.5, phastCons 0.023
Regional constraint	o/e 0.95	unconstrained · MANE · 22 kb · p 0.18 · regional, not allelic
Overall
CADD	7.174	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0906% African / African-American · 68/75,040 alleles

Filtering AF 0.0733% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.067%

Overall 0.00453% 73/1,613,256 alleles · ultra-rare exomes 37/1,460,914 · genomes 36/152,342 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0906%	1,104
Remaining individualsnot grpmax-eligible	0.0064%	15,617
European (non-Finnish)	8.48e-05%	1,179,243

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.Ser203Asn
Coding: c.608G>A
MANE Select: NM_002108
Type: single nucleotide variant
Location: chr12:95992787 (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-ser203asn (accessed [today's date]).

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