Is DYNC2I1 p.Ala600= (c.1800C>T) pathogenic?

DYNC2I1 p.Ala600= (c.1800C>T) is classified Benign in DYNC2I1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-01). Low-frequency (popmax 2.25%, nfe); Associated with short-rib thoracic dysplasia 8 with or without polydactyly.

What condition is associated with DYNC2I1 p.Ala600= (c.1800C>T)?

DYNC2I1 p.Ala600= (c.1800C>T) is associated with short-rib thoracic dysplasia 8 with or without polydactyly (ClinVar).

How common is DYNC2I1 p.Ala600= (c.1800C>T) in the general population?

DYNC2I1 p.Ala600= (c.1800C>T) is low-frequency (popmax 2.25%, nfe) (gnomAD).

DYNC2I1 p.Ala600=

c.1800C>T · rs41271220 · VCV474623

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.25%, nfe)

Conditions

short-rib thoracic dysplasia 8 with or without polydactyly

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -6.6	GERP -4.4
Overall
CADD	0.17	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.25% European (non-Finnish) · 26,509/1,179,658 alleles

Filtering AF 2.22% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.22%

Overall 1.83% 29,453/1,613,468 alleles · low-frequency exomes 27,578/1,461,336 · genomes 1,875/152,132 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	6.03%	17
European (non-Finnish)grpmax	2.25%	45
Remaining individualsnot grpmax-eligible	1.52%	66
Ashkenazi Jewishnot grpmax-eligible	0.804%	124
Admixed American	0.695%	144
Finnishnot grpmax-eligible	0.692%	144
South Asian	0.626%	160
Middle Eastern	0.412%	242
African / African-American	0.324%	309
East Asian	0.00891%	11,218

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala600=
Coding: c.1800C>T
MANE Select: NM_018051
dbSNP: rs41271220
Type: single nucleotide variant
Location: chr7:158918748 (GRCh38)
Gene constraint: LOEUF 0.802 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 62.87 · 4 PDB

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.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
DYNC2I1 p.Ala822Thr 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-ala600 (accessed [today's date]).

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