Is DYNC2I1 p.Ile799Val (c.2395A>G) pathogenic?

DYNC2I1 p.Ile799Val (c.2395A>G) is classified Benign in DYNC2I1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-26). AlphaMissense: likely benign (0.0713); Common (popmax 8.39%, afr) — too common for a highly-penetrant pathogenic allele; Associated with short-rib thoracic dysplasia 8 with or without polydactyly.

What condition is associated with DYNC2I1 p.Ile799Val (c.2395A>G)?

DYNC2I1 p.Ile799Val (c.2395A>G) is associated with short-rib thoracic dysplasia 8 with or without polydactyly (ClinVar).

What do computational predictors say about DYNC2I1 p.Ile799Val (c.2395A>G)?

AlphaMissense predicts likely benign (score 0.0713) — an in-silico prediction, not a clinical call.

DYNC2I1 p.Ile799Val

Q: How common is DYNC2I1 p.Ile799Val (c.2395A>G) in the general population?

DYNC2I1 p.Ile799Val (c.2395A>G) is common (popmax 8.39%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2395A>G · rs61733022 · VCV474627

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0713 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 8.39%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

short-rib thoracic dysplasia 8 with or without polydactyly

Computational evidence

Protein change
AlphaMissense	0.0713	likely benign
REVEL	0.152	moderately benign-leaning
SaProt	LLR -6.10	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -2.7	GERP -4.6
Regional constraint	o/e 0.98	unconstrained · MANE · 89 kb · p 0.52 · regional, not allelic
Overall
CADD	2.497	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 8.39% African / African-American · 6,293/74,964 alleles

Filtering AF 8.22% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.15%

Overall 0.434% 7,004/1,613,352 alleles · common exomes 3,325/1,461,016 · genomes 3,679/152,336 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.39%	12
Remaining individualsnot grpmax-eligible	0.528%	189
Admixed American	0.479%	209
Middle Eastern	0.281%	356
South Asian	0.0187%	5,351
European (non-Finnish)	0.00509%	19,661

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: DYNC2I1
Protein: p.Ile799Val
Coding: c.2395A>G
MANE Select: NM_018051
dbSNP: rs61733022
Type: single nucleotide variant
Location: chr7:158926425 (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 799: 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.Ile799= Benign/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
DYNC2I1 p.Ala800Thr 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-ile799val (accessed [today's date]).

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