Is DYNC1LI2 p.Pro187Ser (c.559C>T) pathogenic?

DYNC1LI2 p.Pro187Ser (c.559C>T) is classified Uncertain significance in DYNC1LI2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-06). AlphaMissense: ambiguous (0.3892); Very rare (popmax 0.000339%, nfe).

How common is DYNC1LI2 p.Pro187Ser (c.559C>T) in the general population?

DYNC1LI2 p.Pro187Ser (c.559C>T) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about DYNC1LI2 p.Pro187Ser (c.559C>T)?

AlphaMissense predicts ambiguous (score 0.3892) — an in-silico prediction, not a clinical call.

DYNC1LI2 p.Pro187Ser

c.559C>T · rs771028906 · VCV2474110

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3892 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3892	ambiguous
REVEL	0.387	indeterminate
SaProt	LLR -5.30	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 28 kb · p 4.8e-08 · regional, not allelic
Overall
CADD	24.2	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 0.000339% European (non-Finnish) · 4/1,179,990 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,613,964 alleles · very rare exomes 4/1,461,826 · genomes 0/152,138 · joint denominator

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.Pro187Ser
Coding: c.559C>T
MANE Select: NM_006141
dbSNP: rs771028906
Type: single nucleotide variant
Location: chr16:66736215 (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.Pro187Leu 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-pro187ser (accessed [today's date]).

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