Is DYNC2H1 p.Pro511= (c.1533A>G) pathogenic?

DYNC2H1 p.Pro511= (c.1533A>G) is classified Likely benign in DYNC2H1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-15). Ultra-rare (popmax 0.0209%, sas); Associated with Jeune syndrome.

What condition is associated with DYNC2H1 p.Pro511= (c.1533A>G)?

DYNC2H1 p.Pro511= (c.1533A>G) is associated with Jeune syndrome (ClinVar).

How common is DYNC2H1 p.Pro511= (c.1533A>G) in the general population?

DYNC2H1 p.Pro511= (c.1533A>G) is ultra-rare (popmax 0.0209%, sas) (gnomAD).

DYNC2H1 p.Pro511=

c.1533A>G · rs780642236 · VCV2905608

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0209%, sas)

Conditions

Jeune syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.36	acceptor loss, 2 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 0.98	GERP -1.4, phastCons 0.98
Overall
CADD	7.24	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0209% South Asian · 19/90,940 alleles

Filtering AF 0.0136% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0114%

Overall 0.0013% 21/1,613,372 alleles · ultra-rare exomes 21/1,461,026 · genomes 0/152,346 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0209%	4,786
Remaining individualsnot grpmax-eligible	0.0032%	31,227

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.Pro511=
Coding: c.1533A>G
MANE Select: NM_001377
dbSNP: rs780642236
Type: single nucleotide variant
Location: chr11:103122872 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 511: the 'stem' region

Full DYNC2H1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Jeune syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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
DYNC2H1 c.12457-1G>C 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-pro511 (accessed [today's date]).

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