Is KMO p.Ser151Tyr (c.452C>A) pathogenic?

KMO p.Ser151Tyr (c.452C>A) is classified Uncertain significance in KMO (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-12). AlphaMissense: likely benign (0.0983); Very rare (popmax 0.00167%, amr).

How common is KMO p.Ser151Tyr (c.452C>A) in the general population?

KMO p.Ser151Tyr (c.452C>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about KMO p.Ser151Tyr (c.452C>A)?

AlphaMissense predicts likely benign (score 0.0983) — an in-silico prediction, not a clinical call.

KMO p.Ser151Tyr

c.452C>A · VCV4044412

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0983 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0983	likely benign
REVEL	0.102	moderately benign-leaning
SaProt	LLR -9.70	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 2.9	GERP 1.1, phastCons 0.99
Regional constraint	o/e 0.83	unconstrained · MANE · 41 kb · p 0.00021 · regional, not allelic
Overall
CADD	23.5	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 0.00167% Admixed American · 1/59,886 alleles

Overall 0.000124% 2/1,613,330 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,886
Remaining individualsnot grpmax-eligible	0.0016%	62,436

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: KMO
Protein: p.Ser151Tyr
Coding: c.452C>A
MANE Select: NM_003679
Type: single nucleotide variant
Location: chr1:241562169 (GRCh38)
Gene constraint: LOEUF 0.755 · pLI 0.15 (gnomAD)
Structure: AlphaFold pLDDT 88.56 · 1 PDB

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

Similar variants

KMO p.Val253Met Uncertain significance ★★ ⚠ same type
KMO c.957+9T>A Benign ★★ same type
KMO c.223-1G>T Uncertain significance ★ same type
KMO p.Arg182Gly Uncertain significance ★ ⚠ same type
KMO p.Arg40Thr Uncertain significance ★ ⚠ same type
KMO p.Arg414Cys Uncertain significance ★ ⚠ same type
KMO p.Arg63Gln Uncertain significance ★ ⚠ same type
KMO p.Asn113His 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/kmo-p-ser151tyr (accessed [today's date]).

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