Is HAO2 p.Ser32Asn (c.95G>A) pathogenic?

HAO2 p.Ser32Asn (c.95G>A) is classified Uncertain significance in HAO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-05). AlphaMissense: likely benign (0.0991); Very rare (popmax 0.00401%, afr).

How common is HAO2 p.Ser32Asn (c.95G>A) in the general population?

HAO2 p.Ser32Asn (c.95G>A) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about HAO2 p.Ser32Asn (c.95G>A)?

AlphaMissense predicts likely benign (score 0.0991) — an in-silico prediction, not a clinical call.

HAO2 p.Ser32Asn

c.95G>A · VCV4268758

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0991 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0991	likely benign
REVEL	0.134	moderately benign-leaning
SaProt	LLR -2.47	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 5	GERP -1.1, phastCons 0.96
Regional constraint	o/e 1.11	unconstrained · MANE · 13 kb · p 0.027 · regional, not allelic
Overall
CADD	9.518	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 0.00401% African / African-American · 3/74,834 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000248% 4/1,609,976 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,945
European (non-Finnish)	8.5e-05%	1,176,356

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: HAO2
Protein: p.Ser32Asn
Coding: c.95G>A
MANE Select: NM_016527
Type: single nucleotide variant
Location: chr1:119381180 (GRCh38)
Gene constraint: LOEUF 1.33 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.99
Residue 32: the fmn hydroxy acid dehydrogenase domain

Full HAO2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

HAO2 p.Ala11Val Uncertain significance ★ ⚠ same type
HAO2 p.Ala120Val Uncertain significance ★ ⚠ same type
HAO2 p.Ala289Thr Uncertain significance ★ same type
HAO2 p.Ala93Gly Uncertain significance ★ ⚠ same type
HAO2 p.Ala98Glu Uncertain significance ★ ⚠ same type
HAO2 p.Arg22Gln Uncertain significance ★ ⚠ same type
HAO2 p.Arg281Gln Uncertain significance ★ ⚠ same type
HAO2 p.Arg301Lys 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/hao2-p-ser32asn (accessed [today's date]).

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