Is DYNC2H1 p.Ala3085Val (c.9254C>T) pathogenic?

DYNC2H1 p.Ala3085Val (c.9254C>T) is classified Conflicting classifications of pathogenicity in DYNC2H1 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-02-04). AlphaMissense: ambiguous (0.5406); Rare (popmax 0.689%, afr); Associated with Jeune syndrome.

What condition is associated with DYNC2H1 p.Ala3085Val (c.9254C>T)?

DYNC2H1 p.Ala3085Val (c.9254C>T) is associated with Jeune syndrome (ClinVar).

How common is DYNC2H1 p.Ala3085Val (c.9254C>T) in the general population?

DYNC2H1 p.Ala3085Val (c.9254C>T) is rare (popmax 0.689%, afr) (gnomAD).

What do computational predictors say about DYNC2H1 p.Ala3085Val (c.9254C>T)?

AlphaMissense predicts ambiguous (score 0.5406) — an in-silico prediction, not a clinical call.

DYNC2H1 p.Ala3085Val

c.9254C>T · rs202071528 · VCV198017

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

ambiguous

0.5406 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.689%, afr)

Conditions

Jeune syndrome

Computational evidence

Protein change
AlphaMissense	0.5406	ambiguous
REVEL	0.71	pathogenic-leaning
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	27.0	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 0.689% African / African-American · 517/75,006 alleles

Filtering AF 0.64% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.621%

Overall 0.0359% 580/1,613,402 alleles · rare exomes 283/1,461,134 · genomes 297/152,268 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.689%	145
Admixed American	0.0483%	2,069
Remaining individualsnot grpmax-eligible	0.0384%	2,602
Middle Eastern	0.033%	3,028
South Asian	0.00329%	30,354
European (non-Finnish)	0.000424%	235,908

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.Ala3085Val
Coding: c.9254C>T
MANE Select: NM_001377
dbSNP: rs202071528
Type: single nucleotide variant
Location: chr11:103222987 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 3085: a turn; the 'stalk' 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-ala3085val (accessed [today's date]).

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