Is UNG p.Ala45Val (c.134C>T) pathogenic?

UNG p.Ala45Val (c.134C>T) is classified Uncertain significance in UNG (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-20). AlphaMissense: likely benign (0.0807); Very rare (popmax 0.00134%, afr); Associated with hyper-IgM syndrome type 5.

What condition is associated with UNG p.Ala45Val (c.134C>T)?

UNG p.Ala45Val (c.134C>T) is associated with hyper-IgM syndrome type 5 (ClinVar).

How common is UNG p.Ala45Val (c.134C>T) in the general population?

UNG p.Ala45Val (c.134C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about UNG p.Ala45Val (c.134C>T)?

AlphaMissense predicts likely benign (score 0.0807) — an in-silico prediction, not a clinical call.

UNG p.Ala45Val

c.134C>T · rs768590866 · VCV1965928

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0807 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hyper-IgM syndrome type 5

Computational evidence

Protein change
AlphaMissense	0.0807	likely benign
REVEL	0.072	moderately benign-leaning
SaProt	LLR -7.10	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.19	GERP 2.5, phastCons 0.2
Regional constraint	o/e 0.98	unconstrained · MANE · 12 kb · p 0.74 · regional, not allelic
Overall
CADD	14.25	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,736 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000373% 6/1,606,796 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,736
South Asian	0.00111%	90,428
European (non-Finnish)	0.00034%	294,234

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.Ala45Val
Coding: c.134C>T
MANE Select: NM_080911
dbSNP: rs768590866
Type: single nucleotide variant
Location: chr12:109098433 (GRCh38)
Gene constraint: LOEUF 1.22 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.52 · 24 PDB
Residue 45: the 'disordered' 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 p.Ala45= Likely benign ★ 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-ala45val (accessed [today's date]).

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