Is UROS p.Pro44Arg (c.131C>G) pathogenic?

UROS p.Pro44Arg (c.131C>G) is classified Uncertain significance in UROS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-01). AlphaMissense: likely benign (0.0972); Ultra-rare (popmax 0.0111%, eas); Associated with Inborn genetic diseases.

What condition is associated with UROS p.Pro44Arg (c.131C>G)?

UROS p.Pro44Arg (c.131C>G) is associated with Inborn genetic diseases (ClinVar).

How common is UROS p.Pro44Arg (c.131C>G) in the general population?

UROS p.Pro44Arg (c.131C>G) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

What do computational predictors say about UROS p.Pro44Arg (c.131C>G)?

AlphaMissense predicts likely benign (score 0.0972) — an in-silico prediction, not a clinical call.

UROS p.Pro44Arg

c.131C>G · rs773818595 · VCV3187006

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0972 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0972	likely benign
REVEL	0.264	benign-leaning
SaProt	LLR -8.42	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 6.3	GERP 1.6, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 28 kb · p 0.22 · regional, not allelic
Overall
CADD	19.33	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 0.0111% East Asian · 5/44,882 alleles

Filtering AF 0.00434% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.00031% 5/1,614,068 alleles · ultra-rare exomes 5/1,461,810 · genomes 0/152,258 · 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: UROS
Protein: p.Pro44Arg
Coding: c.131C>G
MANE Select: NM_000375
dbSNP: rs773818595
Type: single nucleotide variant
Location: chr10:125816193 (GRCh38)
Gene constraint: LOEUF 0.758 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.18 · 3 PDB
Residue 44: an α-helix

Full UROS 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

UROS p.Ala231Thr Uncertain significance ★★ ⚠ same condition
UROS p.Asp113Asn Uncertain significance ★★ ⚠ same condition
UROS p.Asp113His Uncertain significance ★★ ⚠ same condition
UROS p.Gln187Glu Uncertain significance ★★ ⚠ same condition
UROS p.Glu84Ala Uncertain significance ★★ ⚠ same condition
UROS p.Pro138His Uncertain significance ★★ ⚠ same condition
UROS p.Pro18Leu Uncertain significance ★★ ⚠ same condition
UROS p.Tyr128Cys 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/uros-p-pro44arg (accessed [today's date]).

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