Is LIG3 p.Pro233Arg (c.698C>G) pathogenic?

LIG3 p.Pro233Arg (c.698C>G) is classified Uncertain significance in LIG3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-21). AlphaMissense: likely benign (0.1182); Ultra-rare (popmax 0.0109%, nfe); Associated with Inborn genetic diseases.

What condition is associated with LIG3 p.Pro233Arg (c.698C>G)?

LIG3 p.Pro233Arg (c.698C>G) is associated with Inborn genetic diseases (ClinVar).

How common is LIG3 p.Pro233Arg (c.698C>G) in the general population?

LIG3 p.Pro233Arg (c.698C>G) is ultra-rare (popmax 0.0109%, nfe) (gnomAD).

What do computational predictors say about LIG3 p.Pro233Arg (c.698C>G)?

AlphaMissense predicts likely benign (score 0.1182) — an in-silico prediction, not a clinical call.

LIG3 p.Pro233Arg

c.698C>G · rs200240248 · VCV2342269

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1182 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0109%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1182	likely benign
REVEL	0.188	benign-leaning
SaProt	LLR -7.18	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 4.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 21 kb · p 4.7e-07 · regional, not allelic
Overall
CADD	22.2	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 0.0109% European (non-Finnish) · 129/1,179,918 alleles

Filtering AF 0.00936% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0088%

Overall 0.0083% 134/1,613,722 alleles · ultra-rare exomes 122/1,461,690 · genomes 12/152,032 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0109%	9,147
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,796
Remaining individualsnot grpmax-eligible	0.0032%	31,238
Finnishnot grpmax-eligible	0.00156%	63,980

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: LIG3
Protein: p.Pro233Arg
Coding: c.698C>G
MANE Select: NM_013975
dbSNP: rs200240248
Type: single nucleotide variant
Location: chr17:34989472 (GRCh38)
Gene constraint: LOEUF 0.627 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.11 · 13 PDB
Residue 233: a UniProt-annotated variant site (in mtdps20); the 'disordered' region

Full LIG3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LIG3 p.Gln398Arg Uncertain significance ★★ ⚠ same condition
LIG3 p.Ser248Asn Uncertain significance ★★ ⚠ same condition
LIG3 p.Arg942Gln Benign/Likely benign ★★ same condition
LIG3 c.548-1G>C Uncertain significance ★ same condition
LIG3 p.Ala188Val Uncertain significance ★ ⚠ same condition
LIG3 p.Ala271Thr Uncertain significance ★ ⚠ same condition
LIG3 p.Ala432Thr Uncertain significance ★ ⚠ same condition
LIG3 p.Ala458Thr 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/lig3-p-pro233arg (accessed [today's date]).

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