Is UNG p.Lys302= (c.906G>A) pathogenic?

UNG p.Lys302= (c.906G>A) is classified Likely benign in UNG (ClinVar, Single submitter, 2 submitters; last evaluated 2026-01-13). Ultra-rare (popmax 0.0747%, sas); Associated with hyper-IgM syndrome type 5.

What condition is associated with UNG p.Lys302= (c.906G>A)?

UNG p.Lys302= (c.906G>A) is associated with hyper-IgM syndrome type 5 (ClinVar).

How common is UNG p.Lys302= (c.906G>A) in the general population?

UNG p.Lys302= (c.906G>A) is ultra-rare (popmax 0.0747%, sas) (gnomAD).

UNG p.Lys302=

c.906G>A · rs561414480 · VCV1092045

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0747%, sas)

Conditions

hyper-IgM syndrome type 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.292	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP 3.8, phastCons 1
Overall
CADD	11.01	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0747% South Asian · 68/91,086 alleles

Filtering AF 0.0604% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0551%

Overall 0.00471% 76/1,614,170 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0747%	1,340
Remaining individualsnot grpmax-eligible	0.0112%	8,930
European (non-Finnish)	8.47e-05%	1,180,045

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.Lys302=
Coding: c.906G>A
MANE Select: NM_080911
dbSNP: rs561414480
Type: single nucleotide variant
Location: chr12:109109933 (GRCh38)
Gene constraint: LOEUF 1.22 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.52 · 24 PDB
Residue 302: an α-helix

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-lys302 (accessed [today's date]).

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