Is DYNC2H1 p.Arg113Trp (c.337C>T) pathogenic?

DYNC2H1 p.Arg113Trp (c.337C>T) is classified Uncertain significance in DYNC2H1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2023-05-30). AlphaMissense: ambiguous (0.3737); Very rare (popmax 0.00282%, afr); Associated with asphyxiating thoracic dystrophy 3.

What condition is associated with DYNC2H1 p.Arg113Trp (c.337C>T)?

DYNC2H1 p.Arg113Trp (c.337C>T) is associated with asphyxiating thoracic dystrophy 3, Jeune syndrome (ClinVar).

How common is DYNC2H1 p.Arg113Trp (c.337C>T) in the general population?

DYNC2H1 p.Arg113Trp (c.337C>T) is very rare (popmax 0.00282%, afr) (gnomAD).

What do computational predictors say about DYNC2H1 p.Arg113Trp (c.337C>T)?

AlphaMissense predicts ambiguous (score 0.3737) — an in-silico prediction, not a clinical call.

DYNC2H1 p.Arg113Trp

c.337C>T · rs745569868 · VCV302000

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.3737 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00282%, afr)

Conditions

asphyxiating thoracic dystrophy 3

Computational evidence

Protein change
AlphaMissense	0.3737	ambiguous
REVEL	0.296	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.30 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1	GERP -0.34, phastCons 0.45
Regional constraint	o/e 0.99	unconstrained · MANE · 61 kb · p 0.56 · regional, not allelic
Overall
CADD	24.0	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 0.00282% African / African-American · 2/70,992 alleles

Filtering AF 0.000972% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000802%

Overall 0.00142% 22/1,551,176 alleles · very rare exomes 20/1,399,422 · genomes 2/151,754 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00282%	35,496
Admixed American	0.00216%	46,352
European (non-Finnish)	0.00155%	64,323
South Asian	0.00131%	76,590

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.Arg113Trp
Coding: c.337C>T
MANE Select: NM_001377
dbSNP: rs745569868
Type: single nucleotide variant
Location: chr11:103113678 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 113: the 'stem' region

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

Disease context

asphyxiating thoracic dystrophy 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Jeune syndrome

Similar variants

DYNC2H1 p.Arg113= 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
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-arg113trp (accessed [today's date]).

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