Is DYNC2H1 p.Ala3625= (c.10875C>T) pathogenic?

DYNC2H1 p.Ala3625= (c.10875C>T) is classified Likely benign in DYNC2H1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-06). Very rare (popmax 0.00448%, eas); Associated with Jeune syndrome.

What condition is associated with DYNC2H1 p.Ala3625= (c.10875C>T)?

DYNC2H1 p.Ala3625= (c.10875C>T) is associated with Jeune syndrome (ClinVar).

How common is DYNC2H1 p.Ala3625= (c.10875C>T) in the general population?

DYNC2H1 p.Ala3625= (c.10875C>T) is very rare (popmax 0.00448%, eas) (gnomAD).

DYNC2H1 p.Ala3625=

c.10875C>T · rs745497465 · VCV2159386

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00448%, eas)

Conditions

Jeune syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.2	GERP -3.5
Overall
CADD	1.089	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00448% East Asian · 2/44,692 alleles

Filtering AF 0.00107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000608%

Overall 0.00149% 24/1,605,822 alleles · very rare exomes 21/1,453,916 · genomes 3/151,906 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00448%	22,346
African / African-American	0.00402%	24,899
South Asian	0.00223%	44,756
Admixed American	0.00168%	59,486
Remaining individualsnot grpmax-eligible	0.00161%	62,128
European (non-Finnish)	0.00128%	78,356

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.Ala3625=
Coding: c.10875C>T
MANE Select: NM_001377
dbSNP: rs745497465
Type: single nucleotide variant
Location: chr11:103283070 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 3625: an α-helix

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.Ala3625Val 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-ala3625 (accessed [today's date]).

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