Is DYNC2H1 p.His3783Pro (c.11348A>C) pathogenic?

DYNC2H1 p.His3783Pro (c.11348A>C) is classified Uncertain significance in DYNC2H1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-19). AlphaMissense: likely pathogenic (0.8339); Very rare (popmax 0.00334%, amr); Associated with Jeune syndrome.

What condition is associated with DYNC2H1 p.His3783Pro (c.11348A>C)?

DYNC2H1 p.His3783Pro (c.11348A>C) is associated with Jeune syndrome (ClinVar).

How common is DYNC2H1 p.His3783Pro (c.11348A>C) in the general population?

DYNC2H1 p.His3783Pro (c.11348A>C) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about DYNC2H1 p.His3783Pro (c.11348A>C)?

AlphaMissense predicts likely pathogenic (score 0.8339) — an in-silico prediction, not a clinical call.

DYNC2H1 p.His3783Pro

c.11348A>C · rs1431316741 · VCV1721723

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8339 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Jeune syndrome

Computational evidence

Protein change
AlphaMissense	0.8339	likely pathogenic
REVEL	0.786	moderately pathogenic-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this damaging; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 293 kb · p 0.28 · regional, not allelic
Overall
CADD	27.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00334% Admixed American · 2/59,954 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000186% 3/1,613,034 alleles · very rare exomes 3/1,460,780 · genomes 0/152,254 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,977
European (non-Finnish)	8.48e-05%	1,179,306

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.His3783Pro
Coding: c.11348A>C
MANE Select: NM_001377
dbSNP: rs1431316741
Type: single nucleotide variant
Location: chr11:103304686 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 3783: an α-helix; the 'aaa 6' 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-his3783pro (accessed [today's date]).

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