Is UNG p.Ala220= (c.660C>T) pathogenic?

UNG p.Ala220= (c.660C>T) is classified Conflicting classifications of pathogenicity in UNG (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-12-06). Very rare (popmax 0.005%, amr); Associated with hyper-IgM syndrome type 5.

What condition is associated with UNG p.Ala220= (c.660C>T)?

UNG p.Ala220= (c.660C>T) is associated with hyper-IgM syndrome type 5 (ClinVar).

How common is UNG p.Ala220= (c.660C>T) in the general population?

UNG p.Ala220= (c.660C>T) is very rare (popmax 0.005%, amr) (gnomAD).

UNG p.Ala220=

c.660C>T · rs572632781 · VCV306976

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

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 -7.2	GERP -4.2
Overall
CADD	0.428	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,000 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.00197% 3/152,174 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.Ala220=
Coding: c.660C>T
MANE Select: NM_080911
dbSNP: rs572632781
Type: single nucleotide variant
Location: chr12:109103470 (GRCh38)
Gene constraint: LOEUF 1.22 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.52 · 24 PDB

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-ala220 (accessed [today's date]).

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