Is DYNC2H1 p.Arg3622Pro (c.10865G>C) pathogenic?

DYNC2H1 p.Arg3622Pro (c.10865G>C) is classified Uncertain significance in DYNC2H1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-30). AlphaMissense: likely pathogenic (0.9754); Very rare (popmax 0.000765%, nfe); Associated with Jeune syndrome.

What condition is associated with DYNC2H1 p.Arg3622Pro (c.10865G>C)?

DYNC2H1 p.Arg3622Pro (c.10865G>C) is associated with Jeune syndrome (ClinVar).

How common is DYNC2H1 p.Arg3622Pro (c.10865G>C) in the general population?

DYNC2H1 p.Arg3622Pro (c.10865G>C) is very rare (popmax 0.000765%, nfe) (gnomAD).

What do computational predictors say about DYNC2H1 p.Arg3622Pro (c.10865G>C)?

AlphaMissense predicts likely pathogenic (score 0.9754) — an in-silico prediction, not a clinical call.

DYNC2H1 p.Arg3622Pro

c.10865G>C · rs772305401 · VCV1987917

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9754 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000765%, nfe)

Conditions

Jeune syndrome

Computational evidence

Protein change
AlphaMissense	0.9754	likely pathogenic · top 6% in DYNC2H1
REVEL	0.497	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 8.4	GERP 0.94, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 293 kb · p 0.28 · regional, not allelic
Overall
CADD	26.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000765% European (non-Finnish) · 9/1,176,544 alleles

Filtering AF 0.00036% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000261%

Overall 0.00056% 9/1,607,964 alleles · very rare exomes 8/1,455,902 · genomes 1/152,062 · joint denominator

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.Arg3622Pro
Coding: c.10865G>C
MANE Select: NM_001377
dbSNP: rs772305401
Type: single nucleotide variant
Location: chr11:103283060 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 3622: an α-helix

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 p.Arg3622Ter Pathogenic/Likely pathogenic ★★ same residue
DYNC2H1 p.Arg3622= Benign/Likely benign ★★ 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

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-arg3622pro (accessed [today's date]).

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