Is UNG p.Phe11Ser (c.32T>C) pathogenic?

UNG p.Phe11Ser (c.32T>C) is classified Uncertain significance in UNG (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-04-08). AlphaMissense: likely pathogenic (0.7758); Ultra-rare (popmax 0.019%, amr); Associated with hyper-IgM syndrome type 5.

What condition is associated with UNG p.Phe11Ser (c.32T>C)?

UNG p.Phe11Ser (c.32T>C) is associated with hyper-IgM syndrome type 5 (ClinVar).

How common is UNG p.Phe11Ser (c.32T>C) in the general population?

UNG p.Phe11Ser (c.32T>C) is ultra-rare (popmax 0.019%, amr) (gnomAD).

What do computational predictors say about UNG p.Phe11Ser (c.32T>C)?

AlphaMissense predicts likely pathogenic (score 0.7758) — an in-silico prediction, not a clinical call.

UNG p.Phe11Ser

c.32T>C · rs747684225 · VCV947219

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.7758 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.019%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hyper-IgM syndrome type 5

Computational evidence

Protein change
AlphaMissense	0.7758	likely pathogenic
REVEL	0.485	indeterminate
SaProt	LLR -9.87	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 3.3, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 12 kb · p 0.74 · regional, not allelic
Overall
CADD	27.1	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 0.019% Admixed American · 11/57,986 alleles

Filtering AF 0.0152% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0144%

Overall 0.0138% 220/1,595,840 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.019%	5,271
European (non-Finnish)	0.0172%	5,829
Remaining individualsnot grpmax-eligible	0.013%	7,703

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.Phe11Ser
Coding: c.32T>C
MANE Select: NM_080911
dbSNP: rs747684225
Type: single nucleotide variant
Location: chr12:109097711 (GRCh38)
Gene constraint: LOEUF 1.22 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.52 · 24 PDB
Residue 11: the 'disordered' region; the 'interaction with fam72a' region; a functional site (essential for recruitment to s-phase replication foci); the 'mitochondrial localization signal' region

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-phe11ser (accessed [today's date]).

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