Is UBR1 p.Gln1237Pro (c.3710A>C) pathogenic?

UBR1 p.Gln1237Pro (c.3710A>C) is classified Uncertain significance in UBR1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-18). AlphaMissense: likely benign (0.3329); Ultra-rare (popmax 0.0281%, nfe); Associated with Inborn genetic diseases.

What condition is associated with UBR1 p.Gln1237Pro (c.3710A>C)?

UBR1 p.Gln1237Pro (c.3710A>C) is associated with Inborn genetic diseases (ClinVar).

How common is UBR1 p.Gln1237Pro (c.3710A>C) in the general population?

UBR1 p.Gln1237Pro (c.3710A>C) is ultra-rare (popmax 0.0281%, nfe) (gnomAD).

What do computational predictors say about UBR1 p.Gln1237Pro (c.3710A>C)?

AlphaMissense predicts likely benign (score 0.3329) — an in-silico prediction, not a clinical call.

UBR1 p.Gln1237Pro

c.3710A>C · rs375380714 · VCV2196535

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3329 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0281%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3329	likely benign
REVEL	0.105	moderately benign-leaning
SaProt	LLR -7.27	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>C here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.6	GERP 1.5, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 80 kb · p 0.00048 · regional, not allelic
Overall
CADD	23.4	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 0.0281% European (non-Finnish) · 331/1,179,994 alleles

Filtering AF 0.0255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0245%

Overall 0.0215% 347/1,613,928 alleles · ultra-rare exomes 335/1,461,736 · genomes 12/152,192 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0281%	3,565
Remaining individualsnot grpmax-eligible	0.0112%	8,926
Finnishnot grpmax-eligible	0.00938%	10,664
African / African-American	0.004%	24,973

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: UBR1
Protein: p.Gln1237Pro
Coding: c.3710A>C
MANE Select: NM_174916
dbSNP: rs375380714
Type: single nucleotide variant
Location: chr15:42998215 (GRCh38)
Gene constraint: LOEUF 0.47 · pLI 0.97 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.09 · 6 PDB

Full UBR1 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

UBR1 p.Ala1657Val Uncertain significance ★★ ⚠ same condition
UBR1 p.Ala1732Ser Uncertain significance ★★ ⚠ same condition
UBR1 p.Arg1316Gln Uncertain significance ★★ ⚠ same condition
UBR1 p.Arg1716Gln Uncertain significance ★★ ⚠ same condition
UBR1 p.Arg316His Uncertain significance ★★ ⚠ same condition
UBR1 p.Arg367His Uncertain significance ★★ ⚠ same condition
UBR1 p.Arg429Gln Uncertain significance ★★ ⚠ same condition
UBR1 p.Arg621Cys 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/ubr1-p-gln1237pro (accessed [today's date]).

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