Is LIG1 p.Pro11Arg (c.32C>G) pathogenic?

LIG1 p.Pro11Arg (c.32C>G) is classified Uncertain significance in LIG1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-04). AlphaMissense: likely benign (0.1063); Ultra-rare (popmax 0.0133%, afr).

How common is LIG1 p.Pro11Arg (c.32C>G) in the general population?

LIG1 p.Pro11Arg (c.32C>G) is ultra-rare (popmax 0.0133%, afr) (gnomAD).

What do computational predictors say about LIG1 p.Pro11Arg (c.32C>G)?

AlphaMissense predicts likely benign (score 0.1063) — an in-silico prediction, not a clinical call.

LIG1 p.Pro11Arg

c.32C>G · rs143853302 · VCV1403607

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1063 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1063	likely benign
REVEL	0.288	benign-leaning
SaProt	LLR -8.34	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.20	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 9.5	GERP 1.3, phastCons 1
Overall
CADD	25.1	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 0.0133% African / African-American · 10/74,928 alleles

Filtering AF 0.00723% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0055%

Overall 0.000868% 14/1,613,714 alleles · ultra-rare exomes 8/1,461,662 · genomes 6/152,052 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0133%	7,493
Remaining individualsnot grpmax-eligible	0.0064%	15,623

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: LIG1
Protein: p.Pro11Arg
Coding: c.32C>G
MANE Select: NM_000234
dbSNP: rs143853302
Type: single nucleotide variant
Location: chr19:48162337 (GRCh38)
Structure: AlphaFold pLDDT 75.13 · 2 PDB

Full LIG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

LRIG1 p.Ala11Ser Uncertain significance ★ ⚠ same residue
LIG1 p.Pro11= Likely benign ★ same residue
LIG1 p.Ala269Thr Uncertain significance ★★ ⚠ same type
LIG1 p.Ala293Val Uncertain significance ★★ ⚠ same type
LIG1 p.Ala412Thr Uncertain significance ★★ ⚠ same type
LIG1 p.Ala443Thr Uncertain significance ★★ ⚠ same type
LIG1 p.Ala462Ser Uncertain significance ★★ ⚠ same type
LIG1 p.Ala545Gly 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/lig1-p-pro11arg (accessed [today's date]).

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