Is UNG p.Pro52Arg (c.155C>G) pathogenic?

UNG p.Pro52Arg (c.155C>G) is classified Uncertain significance in UNG (ClinVar, Single submitter, 1 submitter; last evaluated 2020-07-15). AlphaMissense: likely benign (0.0417); Very rare (popmax 0.00441%, sas); Associated with hyper-IgM syndrome type 5.

What condition is associated with UNG p.Pro52Arg (c.155C>G)?

UNG p.Pro52Arg (c.155C>G) is associated with hyper-IgM syndrome type 5 (ClinVar).

How common is UNG p.Pro52Arg (c.155C>G) in the general population?

UNG p.Pro52Arg (c.155C>G) is very rare (popmax 0.00441%, sas) (gnomAD).

What do computational predictors say about UNG p.Pro52Arg (c.155C>G)?

AlphaMissense predicts likely benign (score 0.0417) — an in-silico prediction, not a clinical call.

UNG p.Pro52Arg

c.155C>G · rs771026474 · VCV1055136

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0417 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00441%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hyper-IgM syndrome type 5

Computational evidence

Protein change
AlphaMissense	0.0417	likely benign
REVEL	0.068	moderately benign-leaning
SaProt	LLR -3.22	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 5.6	GERP 2.2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 12 kb · p 0.74 · regional, not allelic
Overall
CADD	13.25	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 0.00441% South Asian · 4/90,782 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000893%

Overall 0.00031% 5/1,610,320 alleles · very rare exomes 5/1,457,990 · genomes 0/152,330 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00441%	22,695
European (non-Finnish)	8.48e-05%	1,178,578

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: UNG
Protein: p.Pro52Arg
Coding: c.155C>G
MANE Select: NM_080911
dbSNP: rs771026474
Type: single nucleotide variant
Location: chr12:109098454 (GRCh38)
Gene constraint: LOEUF 1.22 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.52 · 24 PDB
Residue 52: the 'disordered' region

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

Disease context

hyper-IgM syndrome type 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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UNG p.Ala21Thr Uncertain significance ★★ ⚠ same condition
UNG p.Ala87Val Uncertain significance ★★ ⚠ same condition
UNG p.Arg122Ser Uncertain significance ★★ ⚠ same condition
UNG p.Arg269Trp Uncertain significance ★★ ⚠ same condition
UNG p.Asn77Lys Uncertain significance ★★ ⚠ same condition
UNG p.Gln133His 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/ung-p-pro52arg (accessed [today's date]).

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