Is KMO p.Val5Ala (c.14T>C) pathogenic?

KMO p.Val5Ala (c.14T>C) is classified Uncertain significance in KMO (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-16). AlphaMissense: likely benign (0.0632); Ultra-rare (popmax 0.0921%, afr).

How common is KMO p.Val5Ala (c.14T>C) in the general population?

KMO p.Val5Ala (c.14T>C) is ultra-rare (popmax 0.0921%, afr) (gnomAD).

What do computational predictors say about KMO p.Val5Ala (c.14T>C)?

AlphaMissense predicts likely benign (score 0.0632) — an in-silico prediction, not a clinical call.

KMO p.Val5Ala

c.14T>C · rs111476958 · VCV3115953

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0632 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0921%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0632	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -6.37	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 4.4	GERP -0.79, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 17 kb · p 0.34 · regional, not allelic
Overall
CADD	4.686	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 0.0921% African / African-American · 69/74,890 alleles

Filtering AF 0.0746% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0683%

Overall 0.00509% 82/1,611,052 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0921%	1,085
Remaining individualsnot grpmax-eligible	0.016%	6,233
Admixed American	0.00511%	19,579

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.Val5Ala
Coding: c.14T>C
MANE Select: NM_003679
dbSNP: rs111476958
Type: single nucleotide variant
Location: chr1:241532458 (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-val5ala (accessed [today's date]).

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