Is LIG3 p.Pro986Ser (c.2956C>T) pathogenic?

LIG3 p.Pro986Ser (c.2956C>T) is classified Likely benign in LIG3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-15). AlphaMissense: likely benign (0.0722); Rare (popmax 0.584%, eas).

How common is LIG3 p.Pro986Ser (c.2956C>T) in the general population?

LIG3 p.Pro986Ser (c.2956C>T) is rare (popmax 0.584%, eas) (gnomAD).

What do computational predictors say about LIG3 p.Pro986Ser (c.2956C>T)?

AlphaMissense predicts likely benign (score 0.0722) — an in-silico prediction, not a clinical call.

LIG3 p.Pro986Ser

c.2956C>T · VCV3902178

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0722 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.584%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0722	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -5.51	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 -0.29	GERP -1.7
Regional constraint	o/e 0.86	unconstrained · MANE · 21 kb · p 4.7e-07 · regional, not allelic
Overall
CADD	0.252	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

Grpmax group 0.584% East Asian · 262/44,870 alleles

Filtering AF 0.526% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.503%

Overall 0.017% 274/1,614,162 alleles · rare exomes 236/1,461,892 · genomes 38/152,270 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.584%	171
Remaining individualsnot grpmax-eligible	0.0144%	6,945
Admixed American	0.00333%	30,008
South Asian	0.0011%	91,084

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.Pro986Ser
Coding: c.2956C>T
MANE Select: NM_013975
Type: single nucleotide variant
Location: chr17:35004432 (GRCh38)
Gene constraint: LOEUF 0.627 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.11 · 13 PDB
Residue 986: the brct domain; a UniProt-annotated variant site (in mtdps20); a UniProt-annotated variant site (in)

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

Similar variants

LIG3 c.1209-2A>G Pathogenic/Likely pathogenic ★★ same type
LIG3 p.Arg648Gln Uncertain significance ★★ ⚠ same type
LIG3 p.Gln398Arg Uncertain significance ★★ ⚠ same type
LIG3 p.Ser248Asn Uncertain significance ★★ ⚠ same type
LIG3 c.1041+11C>T Benign ★★ same type
LIG3 c.1912-3C>T Benign/Likely benign ★★ same type
LIG3 c.2331+19G>A Benign ★★ same type
LIG3 c.2796+6G>A Likely benign ★★ 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/lig3-p-pro986ser (accessed [today's date]).

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