Is UNG p.Pro196Ser (c.586C>T) pathogenic?

UNG p.Pro196Ser (c.586C>T) is classified Uncertain significance in UNG (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-27). AlphaMissense: likely pathogenic (0.7246); Very rare (popmax 0.00223%, eas); Associated with hyper-IgM syndrome type 5.

What condition is associated with UNG p.Pro196Ser (c.586C>T)?

UNG p.Pro196Ser (c.586C>T) is associated with hyper-IgM syndrome type 5 (ClinVar).

How common is UNG p.Pro196Ser (c.586C>T) in the general population?

UNG p.Pro196Ser (c.586C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about UNG p.Pro196Ser (c.586C>T)?

AlphaMissense predicts likely pathogenic (score 0.7246) — an in-silico prediction, not a clinical call.

UNG p.Pro196Ser

c.586C>T · rs2135886797 · VCV1496922

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7246 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hyper-IgM syndrome type 5

Computational evidence

Protein change
AlphaMissense	0.7246	likely pathogenic
REVEL	0.832	moderately pathogenic-leaning
SaProt	LLR -12.76	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.9	GERP 4.8, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 12 kb · p 0.74 · regional, not allelic
Overall
CADD	27.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00223% East Asian · 1/44,850 alleles

Overall 6.2e-05% 1/1,612,904 alleles · very rare exomes 1/1,461,468 · genomes 0/151,436 · joint denominator

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.Pro196Ser
Coding: c.586C>T
MANE Select: NM_080911
dbSNP: rs2135886797
Type: single nucleotide variant
Location: chr12:109102891 (GRCh38)
Gene constraint: LOEUF 1.22 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.52 · 24 PDB

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-pro196ser (accessed [today's date]).

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