Is KMO p.Pro262Leu (c.785C>T) pathogenic?

KMO p.Pro262Leu (c.785C>T) is classified Likely benign in KMO (ClinVar, Single submitter, 1 submitter; last evaluated 2018-06-01). AlphaMissense: likely benign (0.1125); Rare (popmax 0.675%, sas).

How common is KMO p.Pro262Leu (c.785C>T) in the general population?

KMO p.Pro262Leu (c.785C>T) is rare (popmax 0.675%, sas) (gnomAD).

What do computational predictors say about KMO p.Pro262Leu (c.785C>T)?

AlphaMissense predicts likely benign (score 0.1125) — an in-silico prediction, not a clinical call.

KMO p.Pro262Leu

c.785C>T · rs531693759 · VCV744425

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1125 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.675%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1125	likely benign
REVEL	0.324	indeterminate
SaProt	LLR -13.33	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 1.8	GERP 0.92, phastCons 0.92
Regional constraint	o/e 0.83	unconstrained · MANE · 41 kb · p 0.00021 · regional, not allelic
Overall
CADD	24.0	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 0.675% South Asian · 614/91,016 alleles

Filtering AF 0.63% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.613%

Overall 0.04% 646/1,613,490 alleles · rare exomes 615/1,461,240 · genomes 31/152,250 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.675%	148
Remaining individualsnot grpmax-eligible	0.0368%	2,717
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
African / African-American	0.00133%	74,998
European (non-Finnish)	0.000593%	168,506

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.Pro262Leu
Coding: c.785C>T
MANE Select: NM_003679
dbSNP: rs531693759
Type: single nucleotide variant
Location: chr1:241566588 (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.Pro262= Benign ★ same residue
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

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-pro262leu (accessed [today's date]).

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