Is DYNC2H1 p.Pro3088Ser (c.9262C>T) pathogenic?

DYNC2H1 p.Pro3088Ser (c.9262C>T) is classified Uncertain significance in DYNC2H1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-09-26). AlphaMissense: likely pathogenic (0.8225); Ultra-rare (popmax 0.0142%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DYNC2H1 p.Pro3088Ser (c.9262C>T)?

DYNC2H1 p.Pro3088Ser (c.9262C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DYNC2H1 p.Pro3088Ser (c.9262C>T) in the general population?

DYNC2H1 p.Pro3088Ser (c.9262C>T) is ultra-rare (popmax 0.0142%, nfe) (gnomAD).

What do computational predictors say about DYNC2H1 p.Pro3088Ser (c.9262C>T)?

AlphaMissense predicts likely pathogenic (score 0.8225) — an in-silico prediction, not a clinical call.

DYNC2H1 p.Pro3088Ser

c.9262C>T · rs764931443 · VCV1327629

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.8225 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0142%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8225	likely pathogenic
REVEL	0.514	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 293 kb · p 0.28 · regional, not allelic
Overall
CADD	25.0	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 0.0142% European (non-Finnish) · 168/1,179,564 alleles

Filtering AF 0.0125% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0118%

Overall 0.0108% 174/1,613,264 alleles · ultra-rare exomes 168/1,461,148 · genomes 6/152,116 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0142%	7,021
Remaining individualsnot grpmax-eligible	0.00641%	15,608
East Asian	0.00446%	22,398

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.Pro3088Ser
Coding: c.9262C>T
MANE Select: NM_001377
dbSNP: rs764931443
Type: single nucleotide variant
Location: chr11:103222995 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 3088: an α-helix; the 'stalk' region

Full DYNC2H1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DYNC2H1 p.Pro3088= Likely benign ★ same residue
DYNC2H1 p.Ala1794Ser Uncertain significance ★★ same condition
DYNC2H1 p.Ala1941Pro Uncertain significance ★★ same condition
DYNC2H1 p.Ala2961Val Uncertain significance ★★ ⚠ same condition
DYNC2H1 p.Ala3172Ser Uncertain significance ★★ same condition
DYNC2H1 p.Ala4003Gly Uncertain significance ★★ ⚠ same condition
DYNC2H1 p.Arg1043Cys Uncertain significance ★★ ⚠ same condition
DYNC2H1 p.Arg1153Gln Uncertain significance ★★ 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-pro3088ser (accessed [today's date]).

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