Is DYNC2H1 p.Phe116Ser (c.347T>C) pathogenic?

DYNC2H1 p.Phe116Ser (c.347T>C) is classified Uncertain significance in DYNC2H1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-07). AlphaMissense: likely pathogenic (0.9683); Very rare (popmax 0.000347%, nfe); Associated with Jeune syndrome.

What condition is associated with DYNC2H1 p.Phe116Ser (c.347T>C)?

DYNC2H1 p.Phe116Ser (c.347T>C) is associated with Jeune syndrome (ClinVar).

How common is DYNC2H1 p.Phe116Ser (c.347T>C) in the general population?

DYNC2H1 p.Phe116Ser (c.347T>C) is very rare (popmax 0.000347%, nfe) (gnomAD).

What do computational predictors say about DYNC2H1 p.Phe116Ser (c.347T>C)?

AlphaMissense predicts likely pathogenic (score 0.9683) — an in-silico prediction, not a clinical call.

DYNC2H1 p.Phe116Ser

c.347T>C · rs1020246530 · VCV1405958

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9683 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000347%, nfe)

Conditions

Jeune syndrome

Computational evidence

Protein change
AlphaMissense	0.9683	likely pathogenic · top 7% in DYNC2H1
REVEL	0.353	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.5, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 61 kb · p 0.56 · regional, not allelic
Overall
CADD	26.3	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 0.000347% European (non-Finnish) · 4/1,153,744 alleles

Filtering AF 8.1e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.5e-05%

Overall 0.000259% 4/1,541,636 alleles · very rare exomes 4/1,389,430 · genomes 0/152,206 · joint denominator

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.Phe116Ser
Coding: c.347T>C
MANE Select: NM_001377
dbSNP: rs1020246530
Type: single nucleotide variant
Location: chr11:103113688 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 116: 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 p.Phe116= 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-phe116ser (accessed [today's date]).

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