Is UNG p.Pro172Thr (c.514C>A) pathogenic?

UNG p.Pro172Thr (c.514C>A) is classified Uncertain significance in UNG (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-05). AlphaMissense: likely benign (0.2842); Absent from gnomAD v4.1; Associated with hyper-IgM syndrome type 5.

What condition is associated with UNG p.Pro172Thr (c.514C>A)?

UNG p.Pro172Thr (c.514C>A) is associated with hyper-IgM syndrome type 5 (ClinVar).

How common is UNG p.Pro172Thr (c.514C>A) in the general population?

UNG p.Pro172Thr (c.514C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about UNG p.Pro172Thr (c.514C>A)?

AlphaMissense predicts likely benign (score 0.2842) — an in-silico prediction, not a clinical call.

UNG p.Pro172Thr

c.514C>A · VCV3669348

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2842 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hyper-IgM syndrome type 5

Computational evidence

Protein change
AlphaMissense	0.2842	likely benign
REVEL	0.518	indeterminate
SaProt	LLR -11.88	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.29 · evaluated, not missing
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	26.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: UNG
Protein: p.Pro172Thr
Coding: c.514C>A
MANE Select: NM_080911
Type: single nucleotide variant
Location: chr12:109101980 (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 p.Pro172Ala Uncertain significance ★★ ⚠ same residue
UNG p.Pro172= 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

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-pro172thr (accessed [today's date]).

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