Is UNG p.Pro174= (c.522G>A) pathogenic?

UNG p.Pro174= (c.522G>A) is classified Likely benign in UNG (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-05). Ultra-rare (popmax 0.0666%, afr); Associated with hyper-IgM syndrome type 5.

What condition is associated with UNG p.Pro174= (c.522G>A)?

UNG p.Pro174= (c.522G>A) is associated with hyper-IgM syndrome type 5 (ClinVar).

How common is UNG p.Pro174= (c.522G>A) in the general population?

UNG p.Pro174= (c.522G>A) is ultra-rare (popmax 0.0666%, afr) (gnomAD).

UNG p.Pro174=

c.522G>A · rs148037258 · VCV1094386

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0666%, afr)

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	<0.2	all four deltas below 0.2 · G>C here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP -2.3	GERP -9.7
Overall
CADD	4.265	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0666% African / African-American · 50/75,036 alleles

Filtering AF 0.0519% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0467%

Overall 0.00434% 70/1,613,842 alleles · ultra-rare exomes 46/1,461,558 · genomes 24/152,284 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0666%	1,501
Middle Eastern	0.0168%	5,962
East Asian	0.0134%	7,480
Remaining individualsnot grpmax-eligible	0.008%	12,497
Admixed American	0.005%	20,001
South Asian	0.0022%	45,535
European (non-Finnish)	0.000254%	393,298

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.Pro174=
Coding: c.522G>A
MANE Select: NM_080911
dbSNP: rs148037258
Type: single nucleotide variant
Location: chr12:109101988 (GRCh38)
Gene constraint: LOEUF 1.22 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.52 · 24 PDB
Residue 174: 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 p.Pro174Leu Uncertain significance ★★ ⚠ same residue
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

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-pro174 (accessed [today's date]).

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