Is DYNC2LI1 p.Ala12Pro (c.34G>C) pathogenic?

DYNC2LI1 p.Ala12Pro (c.34G>C) is classified Uncertain significance in DYNC2LI1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-04). AlphaMissense: likely pathogenic (0.8455); Absent from gnomAD v4.1.

How common is DYNC2LI1 p.Ala12Pro (c.34G>C) in the general population?

DYNC2LI1 p.Ala12Pro (c.34G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DYNC2LI1 p.Ala12Pro (c.34G>C)?

AlphaMissense predicts likely pathogenic (score 0.8455) — an in-silico prediction, not a clinical call.

DYNC2LI1 p.Ala12Pro

c.34G>C · rs2467011890 · VCV2111549

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8455 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8455	likely pathogenic
REVEL	0.236	benign-leaning
SaProt	LLR -13.71	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.7	GERP 0.21, phastCons 1
Regional constraint	o/e 1.17	unconstrained · MANE · 36 kb · p 0.00038 · regional, not allelic
Overall
CADD	25.4	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.Ala12Pro
Coding: c.34G>C
MANE Select: NM_016008
dbSNP: rs2467011890
Type: single nucleotide variant
Location: chr2:43776807 (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

Similar variants

DYNC2LI1 p.Leu117Val Pathogenic/Likely pathogenic ★★ ⚠ same type
DYNC2LI1 p.Trp124Ter Pathogenic/Likely pathogenic ★★ same type
ABCG5 p.Ala505Asp Uncertain significance ★★ ⚠ same type
ABCG5 p.Gly288Ser Uncertain significance ★★ ⚠ same type
ABCG5 p.Ser361Cys Uncertain significance ★★ ⚠ same type
ABCG5 p.Val420Gly Uncertain significance ★★ ⚠ same type
DYNC2LI1 p.Cys203Tyr Uncertain significance ★★ same type
DYNC2LI1 p.Glu23Lys 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/dync2li1-p-ala12pro (accessed [today's date]).

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