Is UNG p.Leu165= (c.495C>T) pathogenic?

UNG p.Leu165= (c.495C>T) is classified Likely benign in UNG (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-17). Very rare (popmax 0.000254%, nfe); Associated with hyper-IgM syndrome type 5.

What condition is associated with UNG p.Leu165= (c.495C>T)?

UNG p.Leu165= (c.495C>T) is associated with hyper-IgM syndrome type 5 (ClinVar).

How common is UNG p.Leu165= (c.495C>T) in the general population?

UNG p.Leu165= (c.495C>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

UNG p.Leu165=

c.495C>T · rs2042181358 · VCV2061111

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000254%, 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 0.12	GERP 0.38, phastCons 0.93
Overall
CADD	7.659	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,180,020 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,613,994 alleles · very rare exomes 2/1,461,794 · genomes 1/152,200 · joint denominator

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.Leu165=
Coding: c.495C>T
MANE Select: NM_080911
dbSNP: rs2042181358
Type: single nucleotide variant
Location: chr12:109101961 (GRCh38)
Gene constraint: LOEUF 1.22 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.52 · 24 PDB
Residue 165: a β-strand

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-leu165 (accessed [today's date]).

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