Is DYNC2H1 p.Arg3400Ter (c.10198C>T) pathogenic?

DYNC2H1 p.Arg3400Ter (c.10198C>T) is classified Pathogenic in DYNC2H1 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2025-03-19). Very rare (popmax 0.00267%, afr); Associated with DYNC2H1-related disorder.

What condition is associated with DYNC2H1 p.Arg3400Ter (c.10198C>T)?

DYNC2H1 p.Arg3400Ter (c.10198C>T) is associated with DYNC2H1-related disorder, asphyxiating thoracic dystrophy 3, Jeune syndrome (ClinVar).

How common is DYNC2H1 p.Arg3400Ter (c.10198C>T) in the general population?

DYNC2H1 p.Arg3400Ter (c.10198C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

DYNC2H1 p.Arg3400Ter

c.10198C>T · rs943680446 · VCV423715

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

DYNC2H1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 66 of 89
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.29 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.7	GERP -1.1, phastCons 0.92
Overall
CADD	45.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,802 alleles

Filtering AF 0.000764% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000606%

Overall 0.00261% 42/1,611,574 alleles · very rare exomes 18/1,459,650 · genomes 24/151,924 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	2.31%	43
Remaining individualsnot grpmax-eligible	0.00481%	20,785
African / African-Americangrpmax	0.00267%	37,401
East Asian	0.00223%	44,800
European (non-Finnish)	0.00127%	78,565

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg3400Ter
Coding: c.10198C>T
MANE Select: NM_001377
dbSNP: rs943680446
Type: single nucleotide variant
Location: chr11:103253440 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 3400: an α-helix; the 'aaa 5' region

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

Disease context

Also linked: asphyxiating thoracic dystrophy 3 Jeune syndrome

Similar variants

DYNC2H1 p.Arg3400Gln Conflicting classifications of pathogenicity ★ ⚠ 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-arg3400ter (accessed [today's date]).

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