Is DYNC2H1 p.Phe2377Val (c.7129T>G) pathogenic?

DYNC2H1 p.Phe2377Val (c.7129T>G) is classified Uncertain significance in DYNC2H1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-05-01). AlphaMissense: likely pathogenic (0.8465); Absent from gnomAD v4.1; Associated with Jeune syndrome.

What condition is associated with DYNC2H1 p.Phe2377Val (c.7129T>G)?

DYNC2H1 p.Phe2377Val (c.7129T>G) is associated with Jeune syndrome (ClinVar).

How common is DYNC2H1 p.Phe2377Val (c.7129T>G) in the general population?

DYNC2H1 p.Phe2377Val (c.7129T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DYNC2H1 p.Phe2377Val (c.7129T>G)?

AlphaMissense predicts likely pathogenic (score 0.8465) — an in-silico prediction, not a clinical call.

DYNC2H1 p.Phe2377Val

c.7129T>G · rs1565379048 · VCV558751

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8465 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Jeune syndrome

Computational evidence

Protein change
AlphaMissense	0.8465	likely pathogenic
REVEL	0.549	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 293 kb · p 0.28 · regional, not allelic
Overall
CADD	24.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DYNC2H1
Protein: p.Phe2377Val
Coding: c.7129T>G
MANE Select: NM_001377
dbSNP: rs1565379048
Type: single nucleotide variant
Location: chr11:103187575 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2377: an α-helix; the 'aaa 3' 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.Phe2377fs 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-phe2377val (accessed [today's date]).

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