DYNC2H1 p.Ile3274Phe
c.9820A>T · rs780510358 · VCV2152734
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00505%, amr)
Conditions
1
Jeune syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| REVEL | 0.069 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | Δ0.22 | donor loss, 20 bp away · masked 0 · deltas |
| Constraint at this position | ||
| Conservation | phyloP 9.1 | GERP 1.8, phastCons 1 |
| Regional constraint | o/e 0.98 | unconstrained · MANE · 293 kb · p 0.28 · regional, not allelic |
| Overall | ||
| CADD | 21.2 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00505%
Admixed American · 3/59,420 alleles
Filtering AF
0.00134%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000671%
Overall
0.000251%
4/1,593,622 alleles · very rare
exomes 4/1,441,306 · genomes 0/152,316 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00505% | 19,807 |
| European (non-Finnish) | 8.58e-05% | 1,164,987 |
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
- DYNC2H1
- Protein
- p.Ile3274Phe
- Coding
- c.9820A>T
- MANE Select
- NM_001377 · reported on NM_001080463
- dbSNP
- rs780510358
- Type
- single nucleotide variant
- Location
- chr11:103241527 (GRCh38)
- Gene constraint
- LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Residue 3274
- the 'aaa 5' region
Similar variants
- DYNC2H1 p.Ser3274Arg Likely pathogenic ★ same residue
- DYNC2H1 c.10042+2T>G Pathogenic/Likely pathogenic ★★ same condition
- DYNC2H1 c.10462-2A>G Likely pathogenic ★★ same condition
- DYNC2H1 c.10606-14A>G Pathogenic/Likely pathogenic ★★ same condition
- DYNC2H1 c.10695+1G>A Likely pathogenic ★★ same condition
- DYNC2H1 c.10813-2A>G Likely pathogenic ★★ same condition
- DYNC2H1 c.11493+2T>A Likely pathogenic ★★ same condition
- DYNC2H1 c.11650-1G>A Pathogenic/Likely pathogenic ★★ 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/dync2h1-p-ile3274phe (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown