Is DYNC2H1 p.Ala111Val (c.332C>T) pathogenic?

DYNC2H1 p.Ala111Val (c.332C>T) is classified Uncertain significance in DYNC2H1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-01). AlphaMissense: ambiguous (0.3535); No allele count reported in gnomAD v4.1 (AN 1,564,590); Associated with Jeune syndrome.

What condition is associated with DYNC2H1 p.Ala111Val (c.332C>T)?

DYNC2H1 p.Ala111Val (c.332C>T) is associated with Jeune syndrome (ClinVar).

How common is DYNC2H1 p.Ala111Val (c.332C>T) in the general population?

DYNC2H1 p.Ala111Val (c.332C>T) is no allele count reported in gnomAD v4.1 (AN 1,564,590) (gnomAD).

What do computational predictors say about DYNC2H1 p.Ala111Val (c.332C>T)?

AlphaMissense predicts ambiguous (score 0.3535) — an in-silico prediction, not a clinical call.

DYNC2H1 p.Ala111Val

c.332C>T · VCV4811292

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3535 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,564,590)

Conditions

Jeune syndrome

Computational evidence

Protein change
AlphaMissense	0.3535	ambiguous
REVEL	0.286	benign-leaning
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 0.72, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 61 kb · p 0.56 · regional, not allelic
Overall
CADD	23.4	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

No allele count reported in gnomAD v4.1 (AN 1,564,590). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DYNC2H1
Protein: p.Ala111Val
Coding: c.332C>T
MANE Select: NM_001377
Type: single nucleotide variant
Location: chr11:103113673 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 111: the 'stem' 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 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
DYNC2H1 c.12457-1G>C 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-ala111val (accessed [today's date]).

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