Is LIG3 p.Arg151Trp (c.451C>T) pathogenic?

LIG3 p.Arg151Trp (c.451C>T) is classified Uncertain significance in LIG3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-08). AlphaMissense: likely pathogenic (0.9709); Ultra-rare (popmax 0.0107%, afr); Associated with Inborn genetic diseases.

What condition is associated with LIG3 p.Arg151Trp (c.451C>T)?

LIG3 p.Arg151Trp (c.451C>T) is associated with Inborn genetic diseases (ClinVar).

How common is LIG3 p.Arg151Trp (c.451C>T) in the general population?

LIG3 p.Arg151Trp (c.451C>T) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

What do computational predictors say about LIG3 p.Arg151Trp (c.451C>T)?

AlphaMissense predicts likely pathogenic (score 0.9709) — an in-silico prediction, not a clinical call.

LIG3 p.Arg151Trp

c.451C>T · VCV4097772

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9709 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9709	likely pathogenic
REVEL	0.348	indeterminate
SaProt	LLR -14.36	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 21 kb · p 4.7e-07 · regional, not allelic
Overall
CADD	30.0	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 0.0107% African / African-American · 8/74,860 alleles

Filtering AF 0.00528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.00124% 20/1,613,864 alleles · ultra-rare exomes 11/1,461,848 · genomes 9/152,016 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0107%	9,358
Remaining individualsnot grpmax-eligible	0.0032%	31,235
East Asian	0.00223%	44,902
Admixed American	0.00167%	59,972
European (non-Finnish)	0.000678%	147,502

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.Arg151Trp
Coding: c.451C>T
MANE Select: NM_013975
Type: single nucleotide variant
Location: chr17:34983456 (GRCh38)
Gene constraint: LOEUF 0.627 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.11 · 13 PDB
Residue 151: a UniProt-annotated variant site (in mtdps20)

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.Arg151Gln Likely benign ★ same residue
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

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-arg151trp (accessed [today's date]).

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