Is UNG p.Gln55fs (c.162del) pathogenic?

UNG p.Gln55fs (c.162del) is classified Pathogenic in UNG (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-11). Ultra-rare (popmax 0.0614%, afr); Associated with hyper-IgM syndrome type 5.

What condition is associated with UNG p.Gln55fs (c.162del)?

UNG p.Gln55fs (c.162del) is associated with hyper-IgM syndrome type 5 (ClinVar).

How common is UNG p.Gln55fs (c.162del) in the general population?

UNG p.Gln55fs (c.162del) is ultra-rare (popmax 0.0614%, afr) (gnomAD).

UNG p.Gln55fs

c.162del · rs759483250 · VCV2068429

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0614%, afr)

Conditions

hyper-IgM syndrome type 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -5.6	GERP -9.2
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0614% African / African-American · 46/74,874 alleles

Filtering AF 0.0472% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0423%

Overall 0.00354% 57/1,610,836 alleles · ultra-rare exomes 32/1,458,622 · genomes 25/152,214 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0614%	1,628
Remaining individualsnot grpmax-eligible	0.0144%	6,927
Admixed American	0.00168%	59,694
European (non-Finnish)	8.48e-05%	1,178,924

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.Gln55fs
Coding: c.162del
MANE Select: NM_080911
dbSNP: rs759483250
Type: Deletion
Location: chr12:109098459 (GRCh38)
Gene constraint: LOEUF 1.22 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.52 · 24 PDB
Residue 55: 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

UNG p.Pro131fs Pathogenic/Likely pathogenic ★★ same condition
UNG p.Glu228fs Pathogenic ★ same condition
UNG p.Ile143fs Likely pathogenic ★ same condition
UNG p.Ile190fs Pathogenic ★ same condition
UNG p.Lys184fs Likely pathogenic ★ same condition
UNG p.Phe117fs Pathogenic ★ same condition
UNG p.Ser14fs Pathogenic ★ same condition
UNG p.Ser97_Trp98insTer Pathogenic ★ 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-gln55fs (accessed [today's date]).

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