Is DYNC2H1 p.Arg185His (c.554G>A) pathogenic?

DYNC2H1 p.Arg185His (c.554G>A) is classified Conflicting classifications of pathogenicity in DYNC2H1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-16). AlphaMissense: likely benign (0.0684); Rare (popmax 0.138%, afr); Associated with Inborn genetic diseases.

What condition is associated with DYNC2H1 p.Arg185His (c.554G>A)?

DYNC2H1 p.Arg185His (c.554G>A) is associated with Inborn genetic diseases, asphyxiating thoracic dystrophy 3, Jeune syndrome (ClinVar).

How common is DYNC2H1 p.Arg185His (c.554G>A) in the general population?

DYNC2H1 p.Arg185His (c.554G>A) is rare (popmax 0.138%, afr) (gnomAD).

What do computational predictors say about DYNC2H1 p.Arg185His (c.554G>A)?

AlphaMissense predicts likely benign (score 0.0684) — an in-silico prediction, not a clinical call.

DYNC2H1 p.Arg185His

c.554G>A · rs199960819 · VCV992904

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0684 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.138%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0684	likely benign
REVEL	0.081	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 4.5	GERP 1.3, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 61 kb · p 0.56 · regional, not allelic
Overall
CADD	19.73	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 0.138% African / African-American · 103/74,892 alleles

Filtering AF 0.116% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.108%

Overall 0.00944% 152/1,610,366 alleles · rare exomes 90/1,458,258 · genomes 62/152,108 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.138%	727
East Asian	0.0715%	1,398
Admixed American	0.0067%	14,934
Remaining individualsnot grpmax-eligible	0.00481%	20,787
South Asian	0.00444%	22,527
European (non-Finnish)	0.000509%	196,378

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.Arg185His
Coding: c.554G>A
MANE Select: NM_001377
dbSNP: rs199960819
Type: single nucleotide variant
Location: chr11:103115228 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 185: the 'stem' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: asphyxiating thoracic dystrophy 3 Jeune syndrome

Similar variants

DYNC2H1 p.Arg185Cys Uncertain significance ★★ ⚠ 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-arg185his (accessed [today's date]).

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