Is DYNC2H1 p.Ala3165= (c.9495A>G) pathogenic?

DYNC2H1 p.Ala3165= (c.9495A>G) is classified Likely benign in DYNC2H1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-10). Very rare (popmax 0.00751%, amr); Associated with Jeune syndrome.

What condition is associated with DYNC2H1 p.Ala3165= (c.9495A>G)?

DYNC2H1 p.Ala3165= (c.9495A>G) is associated with Jeune syndrome (ClinVar).

How common is DYNC2H1 p.Ala3165= (c.9495A>G) in the general population?

DYNC2H1 p.Ala3165= (c.9495A>G) is very rare (popmax 0.00751%, amr) (gnomAD).

DYNC2H1 p.Ala3165=

c.9495A>G · rs778791349 · VCV1941069

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00751%, amr)

Conditions

Jeune syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.022	GERP -3.6, phastCons 0.039
Overall
CADD	6.52	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00751% Admixed American · 4/53,282 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00148%

Overall 0.000319% 5/1,568,954 alleles · very rare exomes 5/1,416,960 · genomes 0/151,994 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00751%	13,320
Remaining individualsnot grpmax-eligible	0.00164%	60,820

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.Ala3165=
Coding: c.9495A>G
MANE Select: NM_001377
dbSNP: rs778791349
Type: single nucleotide variant
Location: chr11:103234088 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 3165: an α-helix; the 'stalk' 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 p.Ala3165fs Pathogenic ★ 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-ala3165 (accessed [today's date]).

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