Is UNG p.Ser97= (c.291C>T) pathogenic?

UNG p.Ser97= (c.291C>T) is classified Benign in UNG (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-27). Low-frequency (popmax 2.12%, afr); Associated with hyper-IgM syndrome type 5.

What condition is associated with UNG p.Ser97= (c.291C>T)?

UNG p.Ser97= (c.291C>T) is associated with hyper-IgM syndrome type 5 (ClinVar).

How common is UNG p.Ser97= (c.291C>T) in the general population?

UNG p.Ser97= (c.291C>T) is low-frequency (popmax 2.12%, afr) (gnomAD).

UNG p.Ser97=

c.291C>T · rs3219210 · VCV463871

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.12%, 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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.4	GERP -4.5
Overall
CADD	7.607	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.12% African / African-American · 1,588/75,046 alleles

Filtering AF 2.03% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.99%

Overall 0.122% 1,965/1,613,492 alleles · low-frequency exomes 1,080/1,461,162 · genomes 885/152,330 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.12%	47
Middle Eastern	0.528%	189
Remaining individualsnot grpmax-eligible	0.173%	579
Admixed American	0.157%	639
South Asian	0.0143%	7,006
European (non-Finnish)	0.011%	9,077

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.Ser97=
Coding: c.291C>T
MANE Select: NM_080911
dbSNP: rs3219210
Type: single nucleotide variant
Location: chr12:109098590 (GRCh38)
Gene constraint: LOEUF 1.22 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.52 · 24 PDB
Residue 97: 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.Ser97_Trp98insTer Pathogenic ★ same residue
UNG p.Ser97Cys 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

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-ser97 (accessed [today's date]).

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