Is DYNC1LI2 p.Pro187Leu (c.560C>T) pathogenic?

DYNC1LI2 p.Pro187Leu (c.560C>T) is classified Uncertain significance in DYNC1LI2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-24). AlphaMissense: likely benign (0.2831); Ultra-rare (popmax 0.01%, amr).

How common is DYNC1LI2 p.Pro187Leu (c.560C>T) in the general population?

DYNC1LI2 p.Pro187Leu (c.560C>T) is ultra-rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about DYNC1LI2 p.Pro187Leu (c.560C>T)?

AlphaMissense predicts likely benign (score 0.2831) — an in-silico prediction, not a clinical call.

DYNC1LI2 p.Pro187Leu

c.560C>T · VCV4662669

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2831 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2831	likely benign
REVEL	0.387	indeterminate
SaProt	LLR -6.36	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 28 kb · p 4.8e-08 · regional, not allelic
Overall
CADD	26.5	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 0.01% Admixed American · 6/59,990 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.00041% 6/1,461,856 alleles · ultra-rare

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: DYNC1LI2
Protein: p.Pro187Leu
Coding: c.560C>T
MANE Select: NM_006141
Type: single nucleotide variant
Location: chr16:66736214 (GRCh38)
Gene constraint: LOEUF 0.474 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.62 · 24 PDB
Residue 187: the 'disordered' region

Full DYNC1LI2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DYNC1LI2 p.Pro187Ser Uncertain significance ★ ⚠ same residue
DYNC1LI2 p.Ala122Ser Uncertain significance ★ ⚠ same type
DYNC1LI2 p.Ala153Gly Uncertain significance ★ ⚠ same type
DYNC1LI2 p.Ala22Val Uncertain significance ★ ⚠ same type
DYNC1LI2 p.Arg103Cys Uncertain significance ★ ⚠ same type
DYNC1LI2 p.Arg157Cys Uncertain significance ★ ⚠ same type
DYNC1LI2 p.Arg157His Uncertain significance ★ ⚠ same type
DYNC1LI2 p.Arg175Gln 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/dync1li2-p-pro187leu (accessed [today's date]).

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