Is KMO p.Pro200Ser (c.598C>T) pathogenic?

KMO p.Pro200Ser (c.598C>T) is classified Benign in KMO (ClinVar, Single submitter, 1 submitter; last evaluated 2018-06-01). AlphaMissense: likely benign (0.1385); Low-frequency (popmax 1.07%, sas).

How common is KMO p.Pro200Ser (c.598C>T) in the general population?

KMO p.Pro200Ser (c.598C>T) is low-frequency (popmax 1.07%, sas) (gnomAD).

What do computational predictors say about KMO p.Pro200Ser (c.598C>T)?

AlphaMissense predicts likely benign (score 0.1385) — an in-silico prediction, not a clinical call.

KMO p.Pro200Ser

c.598C>T · rs568398307 · VCV721466

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1385 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.07%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1385	likely benign
REVEL	0.41	indeterminate
SaProt	LLR -11.23	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 0.93, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 41 kb · p 0.00021 · regional, not allelic
Overall
CADD	25.4	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 1.07% South Asian · 972/91,076 alleles

Filtering AF 1.01% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.989%

Overall 0.0665% 1,073/1,614,064 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	1.07%	94
Middle Eastern	0.116%	866
Remaining individualsnot grpmax-eligible	0.104%	962
African / African-American	0.00267%	37,517
East Asian	0.00223%	44,884
European (non-Finnish)	0.00212%	47,198
Admixed American	0.00167%	60,014

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.Pro200Ser
Coding: c.598C>T
MANE Select: NM_003679
dbSNP: rs568398307
Type: single nucleotide variant
Location: chr1:241562315 (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-pro200ser (accessed [today's date]).

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