Is UNG p.Ile182Val (c.544A>G) pathogenic?

UNG p.Ile182Val (c.544A>G) is classified Uncertain significance in UNG (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-02-17). AlphaMissense: likely benign (0.2467); Rare (popmax 0.186%, sas); Associated with hyper-IgM syndrome type 5.

What condition is associated with UNG p.Ile182Val (c.544A>G)?

UNG p.Ile182Val (c.544A>G) is associated with hyper-IgM syndrome type 5 (ClinVar).

How common is UNG p.Ile182Val (c.544A>G) in the general population?

UNG p.Ile182Val (c.544A>G) is rare (popmax 0.186%, sas) (gnomAD).

What do computational predictors say about UNG p.Ile182Val (c.544A>G)?

AlphaMissense predicts likely benign (score 0.2467) — an in-silico prediction, not a clinical call.

UNG p.Ile182Val

c.544A>G · rs545691651 · VCV306974

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.2467 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.186%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hyper-IgM syndrome type 5

Computational evidence

Protein change
AlphaMissense	0.2467	likely benign
REVEL	0.656	pathogenic-leaning
SaProt	LLR -10.21	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 4.8, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 12 kb · p 0.74 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.186% South Asian · 169/91,028 alleles

Filtering AF 0.163% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.154%

Overall 0.0109% 175/1,612,786 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.186%	539
Middle Eastern	0.0165%	6,054
Remaining individualsnot grpmax-eligible	0.0064%	15,617
Admixed American	0.00167%	59,950

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.Ile182Val
Coding: c.544A>G
MANE Select: NM_080911
dbSNP: rs545691651
Type: single nucleotide variant
Location: chr12:109102849 (GRCh38)
Gene constraint: LOEUF 1.22 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.52 · 24 PDB
Residue 182: 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-ile182val (accessed [today's date]).

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