Is UNG p.Ser97Cys (c.289A>T) pathogenic?

UNG p.Ser97Cys (c.289A>T) is classified Uncertain significance in UNG (ClinVar, Single submitter, 1 submitter; last evaluated 2020-08-01). AlphaMissense: likely benign (0.258); Absent from gnomAD v4.1; Associated with hereditary breast ovarian cancer syndrome.

What condition is associated with UNG p.Ser97Cys (c.289A>T)?

UNG p.Ser97Cys (c.289A>T) is associated with hereditary breast ovarian cancer syndrome (ClinVar).

How common is UNG p.Ser97Cys (c.289A>T) in the general population?

UNG p.Ser97Cys (c.289A>T) is absent from gnomAD v4.1 (gnomAD).

How is Hereditary breast and/or ovarian cancer syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about UNG p.Ser97Cys (c.289A>T)?

AlphaMissense predicts likely benign (score 0.258) — an in-silico prediction, not a clinical call.

UNG p.Ser97Cys

c.289A>T · rs2135882458 · VCV981858

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.258 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary breast ovarian cancer syndrome

Computational evidence

Protein change
AlphaMissense	0.258	likely benign
REVEL	0.663	pathogenic-leaning
SaProt	LLR -11.83	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.2	GERP 4.5, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 12 kb · p 0.74 · regional, not allelic
Overall
CADD	24.5	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.Ser97Cys
Coding: c.289A>T
MANE Select: NM_080911
dbSNP: rs2135882458
Type: single nucleotide variant
Location: chr12:109098588 (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

hereditary breast ovarian cancer syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary breast and/or ovarian cancer syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

UNG p.Ser97= Benign ★★ same residue
UNG p.Ser97_Trp98insTer Pathogenic ★ same residue
UNG c.623-9T>A Uncertain significance ★★ same type
UNG c.801+5G>A Uncertain significance ★★ same type
UNG p.Ala21Thr Uncertain significance ★★ ⚠ same type
UNG p.Ala87Val Uncertain significance ★★ ⚠ same type
UNG p.Arg122Ser Uncertain significance ★★ ⚠ same type
UNG p.Arg269Trp Uncertain significance ★★ ⚠ same type

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-ser97cys (accessed [today's date]).

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