Is UMPS p.Ile447Val (c.1339A>G) pathogenic?

UMPS p.Ile447Val (c.1339A>G) is classified Uncertain significance in UMPS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-10). AlphaMissense: likely benign (0.103); Very rare (popmax 0.00127%, nfe); Associated with Inborn genetic diseases.

What condition is associated with UMPS p.Ile447Val (c.1339A>G)?

UMPS p.Ile447Val (c.1339A>G) is associated with Inborn genetic diseases (ClinVar).

How common is UMPS p.Ile447Val (c.1339A>G) in the general population?

UMPS p.Ile447Val (c.1339A>G) is very rare (popmax 0.00127%, nfe) (gnomAD).

What do computational predictors say about UMPS p.Ile447Val (c.1339A>G)?

AlphaMissense predicts likely benign (score 0.103) — an in-silico prediction, not a clinical call.

UMPS p.Ile447Val

c.1339A>G · rs1278382088 · VCV2475045

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.103 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00127%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.103	likely benign
REVEL	0.257	benign-leaning
SaProt	LLR -8.62	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.1	GERP 1.6, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 14 kb · p 0.016 · regional, not allelic
Overall
CADD	23.6	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 0.00127% European (non-Finnish) · 15/1,180,046 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.000929% 15/1,614,130 alleles · very rare exomes 14/1,461,866 · genomes 1/152,264 · joint denominator

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: UMPS
Protein: p.Ile447Val
Coding: c.1339A>G
MANE Select: NM_000373
dbSNP: rs1278382088
Type: single nucleotide variant
Location: chr3:124743980 (GRCh38)
Gene constraint: LOEUF 0.735 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.36 · 125 PDB
Residue 447: the 'ompdecase' region; a β-strand

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

UMPS p.Ala386Val Uncertain significance ★★ ⚠ same condition
UMPS p.Cys72Phe Uncertain significance ★★ ⚠ same condition
UMPS p.Ile318Thr Uncertain significance ★★ ⚠ same condition
UMPS p.Val12Gly Uncertain significance ★★ ⚠ same condition
UMPS p.Leu120= Likely benign ★★ same condition
UMPS p.Ala165Val Uncertain significance ★ ⚠ same condition
UMPS p.Ala208Val Uncertain significance ★ ⚠ same condition
UMPS p.Ala2Val Uncertain significance ★ ⚠ same condition

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/umps-p-ile447val (accessed [today's date]).

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