Is HAO1 p.Ser100Phe (c.299C>T) pathogenic?

HAO1 p.Ser100Phe (c.299C>T) is classified Uncertain significance in HAO1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-30). AlphaMissense: likely benign (0.1357); Very rare (popmax 0.000339%, nfe).

How common is HAO1 p.Ser100Phe (c.299C>T) in the general population?

HAO1 p.Ser100Phe (c.299C>T) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about HAO1 p.Ser100Phe (c.299C>T)?

AlphaMissense predicts likely benign (score 0.1357) — an in-silico prediction, not a clinical call.

HAO1 p.Ser100Phe

c.299C>T · VCV3283452

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1357 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1357	likely benign
REVEL	0.217	benign-leaning
SaProt	LLR -11.24	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 57 kb · p 0.5 · regional, not allelic
Overall
CADD	22.0	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 0.000339% European (non-Finnish) · 4/1,179,550 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,613,152 alleles · very rare exomes 3/1,460,996 · genomes 1/152,156 · 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: HAO1
Protein: p.Ser100Phe
Coding: c.299C>T
MANE Select: NM_017545
Type: single nucleotide variant
Location: chr20:7914410 (GRCh38)
Gene constraint: LOEUF 1.219 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.55 · 21 PDB
Residue 100: the fmn hydroxy acid dehydrogenase domain; an α-helix

Full HAO1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

HAO1 p.Gly165Cys Pathogenic ★ same type
HAO1 p.Ala210Ser Uncertain significance ★ ⚠ same type
HAO1 p.Ala244Thr Uncertain significance ★ same type
HAO1 p.Ala345Val Uncertain significance ★ ⚠ same type
HAO1 p.Ala366Pro Uncertain significance ★ ⚠ same type
HAO1 p.Ala81Thr Uncertain significance ★ ⚠ same type
HAO1 p.Arg127Cys Uncertain significance ★ ⚠ same type
HAO1 p.Arg137Gln 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/hao1-p-ser100phe (accessed [today's date]).

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