Is UNG p.Ser14fs (c.39del) pathogenic?

UNG p.Ser14fs (c.39del) is classified Pathogenic in UNG (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-15). Absent from gnomAD v4.1; Associated with hyper-IgM syndrome type 5.

What condition is associated with UNG p.Ser14fs (c.39del)?

UNG p.Ser14fs (c.39del) is associated with hyper-IgM syndrome type 5 (ClinVar).

How common is UNG p.Ser14fs (c.39del) in the general population?

UNG p.Ser14fs (c.39del) is absent from gnomAD v4.1 (gnomAD).

UNG p.Ser14fs

c.39del · rs2499976292 · VCV2083377

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,584,012)

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 1 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.81	GERP 3.3, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,584,012). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: UNG
Protein: p.Ser14fs
Coding: c.39del
MANE Select: NM_080911
dbSNP: rs2499976292
Type: Deletion
Location: chr12:109097714 (GRCh38)
Gene constraint: LOEUF 1.22 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.52 · 24 PDB
Residue 14: the 'disordered' region; the 'interaction with fam72a' region; a modified residue (phosphoserine); the 'mitochondrial localization signal' 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.Gln55fs Pathogenic ★★ same condition
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.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-ser14fs (accessed [today's date]).

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