Is DYNC2LI1 p.Leu145Pro (c.434T>C) pathogenic?

DYNC2LI1 p.Leu145Pro (c.434T>C) is classified Uncertain significance in DYNC2LI1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-08). AlphaMissense: ambiguous (0.4417); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DYNC2LI1 p.Leu145Pro (c.434T>C)?

DYNC2LI1 p.Leu145Pro (c.434T>C) is associated with Inborn genetic diseases (ClinVar).

How common is DYNC2LI1 p.Leu145Pro (c.434T>C) in the general population?

DYNC2LI1 p.Leu145Pro (c.434T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DYNC2LI1 p.Leu145Pro (c.434T>C)?

AlphaMissense predicts ambiguous (score 0.4417) — an in-silico prediction, not a clinical call.

DYNC2LI1 p.Leu145Pro

c.434T>C · VCV4618174

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4417 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4417	ambiguous
REVEL	0.287	benign-leaning
SaProt	LLR -14.22	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.8	GERP 2.5, phastCons 1
Regional constraint	o/e 1.17	unconstrained · MANE · 36 kb · p 0.00038 · regional, not allelic
Overall
CADD	24.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DYNC2LI1
Protein: p.Leu145Pro
Coding: c.434T>C
MANE Select: NM_016008
Type: single nucleotide variant
Location: chr2:43794570 (GRCh38)
Gene constraint: LOEUF 1.028 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.49 · 3 PDB

Full DYNC2LI1 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

DYNC2LI1 p.Cys203Tyr Uncertain significance ★★ same condition
DYNC2LI1 p.Glu23Lys Uncertain significance ★★ ⚠ same condition
DYNC2LI1 p.Gly24Asp Uncertain significance ★★ ⚠ same condition
DYNC2LI1 p.Gly88Ser Uncertain significance ★★ ⚠ same condition
DYNC2LI1 p.Ile184Thr Uncertain significance ★★ same condition
DYNC2LI1 p.Pro254Leu Uncertain significance ★★ ⚠ same condition
DYNC2LI1 p.Tyr213Cys Uncertain significance ★★ ⚠ same condition
DYNC2LI1 p.Val114Ile 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/dync2li1-p-leu145pro (accessed [today's date]).

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