Is UNG p.Ile2= (c.6C>A) pathogenic?

UNG p.Ile2= (c.6C>A) is classified Uncertain significance in UNG (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). Very rare (popmax 0.00051%, nfe); Associated with hyper-IgM syndrome type 5.

What condition is associated with UNG p.Ile2= (c.6C>A)?

UNG p.Ile2= (c.6C>A) is associated with hyper-IgM syndrome type 5 (ClinVar).

How common is UNG p.Ile2= (c.6C>A) in the general population?

UNG p.Ile2= (c.6C>A) is very rare (popmax 0.00051%, nfe) (gnomAD).

UNG p.Ile2=

c.6C>A · rs886048905 · VCV306965

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00051%, nfe)

Conditions

hyper-IgM syndrome type 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.27	GERP -0.87, phastCons 0.25
Overall
CADD	11.71	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00051% European (non-Finnish) · 6/1,175,752 alleles

Filtering AF 0.000184% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000121%

Overall 0.000413% 6/1,452,422 alleles · very rare

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.Ile2=
Coding: c.6C>A
MANE Select: NM_080911
dbSNP: rs886048905
Type: single nucleotide variant
Location: chr12:109097685 (GRCh38)
Gene constraint: LOEUF 1.22 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.52 · 24 PDB
Residue 2: the 'disordered' region; the 'interaction with fam72a' region; 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 c.623-9T>A Uncertain significance ★★ same condition
UNG c.801+5G>A Uncertain significance ★★ same condition
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-ile2 (accessed [today's date]).

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