Is DYNC2H1 p.Ser2128Phe (c.6383C>T) pathogenic?

DYNC2H1 p.Ser2128Phe (c.6383C>T) is classified Uncertain significance in DYNC2H1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-21). AlphaMissense: ambiguous (0.4359); Very rare (popmax 0.00135%, afr); Associated with Jeune syndrome.

What condition is associated with DYNC2H1 p.Ser2128Phe (c.6383C>T)?

DYNC2H1 p.Ser2128Phe (c.6383C>T) is associated with Jeune syndrome (ClinVar).

How common is DYNC2H1 p.Ser2128Phe (c.6383C>T) in the general population?

DYNC2H1 p.Ser2128Phe (c.6383C>T) is very rare (popmax 0.00135%, afr) (gnomAD).

What do computational predictors say about DYNC2H1 p.Ser2128Phe (c.6383C>T)?

AlphaMissense predicts ambiguous (score 0.4359) — an in-silico prediction, not a clinical call.

DYNC2H1 p.Ser2128Phe

c.6383C>T · rs769771518 · VCV2128921

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4359 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00135%, afr)

Conditions

Jeune syndrome

Computational evidence

Protein change
AlphaMissense	0.4359	ambiguous
REVEL	0.79	moderately pathogenic-leaning
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.6, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 8,693 bp · p 6.7e-06 · regional, not allelic
Overall
CADD	24.1	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 0.00135% African / African-American · 1/73,984 alleles

Overall 0.000127% 2/1,573,632 alleles · very rare exomes 1/1,422,038 · genomes 1/151,594 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00135%	73,984
South Asian	0.00116%	86,116

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.Ser2128Phe
Coding: c.6383C>T
MANE Select: NM_001377
dbSNP: rs769771518
Type: single nucleotide variant
Location: chr11:103181792 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2128: an α-helix; the 'aaa 2' 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.Ser2128_Trp2129insTer 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-ser2128phe (accessed [today's date]).

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