Is DYNC2I1 p.Ala1007Thr (c.3019G>A) pathogenic?

DYNC2I1 p.Ala1007Thr (c.3019G>A) is classified Uncertain significance in DYNC2I1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-29). AlphaMissense: likely benign (0.076); Absent from gnomAD v4.1; Associated with short-rib thoracic dysplasia 8 with or without polydactyly.

What condition is associated with DYNC2I1 p.Ala1007Thr (c.3019G>A)?

DYNC2I1 p.Ala1007Thr (c.3019G>A) is associated with short-rib thoracic dysplasia 8 with or without polydactyly (ClinVar).

How common is DYNC2I1 p.Ala1007Thr (c.3019G>A) in the general population?

DYNC2I1 p.Ala1007Thr (c.3019G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DYNC2I1 p.Ala1007Thr (c.3019G>A)?

AlphaMissense predicts likely benign (score 0.076) — an in-silico prediction, not a clinical call.

DYNC2I1 p.Ala1007Thr

c.3019G>A · rs1851807467 · VCV2182615

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.076 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

short-rib thoracic dysplasia 8 with or without polydactyly

Computational evidence

Protein change
AlphaMissense	0.076	likely benign
REVEL	0.011	strongly benign-leaning
SaProt	LLR -6.18	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 -0.089	GERP -4.1
Regional constraint	o/e 0.98	unconstrained · MANE · 89 kb · p 0.52 · regional, not allelic
Overall
CADD	12.0	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

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: DYNC2I1
Protein: p.Ala1007Thr
Coding: c.3019G>A
MANE Select: NM_018051
dbSNP: rs1851807467
Type: single nucleotide variant
Location: chr7:158945597 (GRCh38)
Gene constraint: LOEUF 0.802 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 62.87 · 4 PDB
Residue 1007: a UniProt-annotated variant site (in srtd8; reduces interaction with ift proteins); a UniProt-annotated variant site (in srtd8)

Full DYNC2I1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

short-rib thoracic dysplasia 8 with or without polydactyly — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DYNC2I1 p.Ala1007Val Conflicting classifications of pathogenicity ★ ⚠ same residue
DYNC2I1 p.Ala1007= Likely benign ★ same residue
DYNC2I1 p.Arg228Ter Pathogenic/Likely pathogenic ★★ same condition
DYNC2I1 p.Arg441Ter Pathogenic/Likely pathogenic ★★ same condition
DYNC2I1 p.Arg642Ter Pathogenic/Likely pathogenic ★★ same condition
DYNC2I1 p.Arg762Ter Pathogenic ★★ same condition
DYNC2I1 p.Ala157Val Uncertain significance ★★ ⚠ same condition
DYNC2I1 p.Ala609Val 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/dync2i1-p-ala1007thr (accessed [today's date]).

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