Is KMO p.Arg464Trp (c.1390C>T) pathogenic?

KMO p.Arg464Trp (c.1390C>T) is classified Likely benign in KMO (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-16). AlphaMissense: likely benign (0.0734); Very rare (popmax 0.00333%, amr).

How common is KMO p.Arg464Trp (c.1390C>T) in the general population?

KMO p.Arg464Trp (c.1390C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about KMO p.Arg464Trp (c.1390C>T)?

AlphaMissense predicts likely benign (score 0.0734) — an in-silico prediction, not a clinical call.

KMO p.Arg464Trp

c.1390C>T · rs749019145 · VCV2468990

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0734 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0734	likely benign
REVEL	0.068	moderately benign-leaning
SaProt	LLR -6.12	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 -0.064	GERP -3.5
Regional constraint	o/e 0.83	unconstrained · MANE · 41 kb · p 0.00021 · regional, not allelic
Overall
CADD	7.316	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 0.00333% Admixed American · 2/60,006 alleles

Filtering AF 0.00172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00149%

Overall 0.00217% 35/1,613,942 alleles · very rare exomes 32/1,461,776 · genomes 3/152,166 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,003
Remaining individualsnot grpmax-eligible	0.0032%	31,251
European (non-Finnish)	0.00246%	40,689
South Asian	0.0022%	45,537

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.Arg464Trp
Coding: c.1390C>T
MANE Select: NM_003679
dbSNP: rs749019145
Type: single nucleotide variant
Location: chr1:241592082 (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-arg464trp (accessed [today's date]).

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