Is DYNC2H1 p.Asp2184Val (c.6551A>T) pathogenic?

DYNC2H1 p.Asp2184Val (c.6551A>T) is classified Conflicting classifications of pathogenicity in DYNC2H1 (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-01-18). AlphaMissense: likely benign (0.1608); Rare (popmax 0.296%, afr); Associated with Jeune syndrome.

What condition is associated with DYNC2H1 p.Asp2184Val (c.6551A>T)?

DYNC2H1 p.Asp2184Val (c.6551A>T) is associated with Jeune syndrome (ClinVar).

How common is DYNC2H1 p.Asp2184Val (c.6551A>T) in the general population?

DYNC2H1 p.Asp2184Val (c.6551A>T) is rare (popmax 0.296%, afr) (gnomAD).

What do computational predictors say about DYNC2H1 p.Asp2184Val (c.6551A>T)?

AlphaMissense predicts likely benign (score 0.1608) — an in-silico prediction, not a clinical call.

DYNC2H1 p.Asp2184Val

c.6551A>T · rs201967064 · VCV281769

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.1608 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.296%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Jeune syndrome

Computational evidence

Protein change
AlphaMissense	0.1608	likely benign
REVEL	0.129	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.5, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 8,693 bp · p 6.7e-06 · regional, not allelic
Overall
CADD	21.0	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 0.296% African / African-American · 222/74,896 alleles

Filtering AF 0.264% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.252%

Overall 0.0149% 240/1,611,332 alleles · rare exomes 99/1,459,298 · genomes 141/152,034 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.296%	337
Remaining individualsnot grpmax-eligible	0.0144%	6,926
Admixed American	0.0134%	7,477
European (non-Finnish)	8.49e-05%	1,178,155

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.Asp2184Val
Coding: c.6551A>T
MANE Select: NM_001377
dbSNP: rs201967064
Type: single nucleotide variant
Location: chr11:103184969 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)

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-asp2184val (accessed [today's date]).

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