Is DYNC2H1 p.Val3137Phe (c.9409G>T) pathogenic?

DYNC2H1 p.Val3137Phe (c.9409G>T) is classified Uncertain significance in DYNC2H1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-19). AlphaMissense: ambiguous (0.3829); Very rare (popmax 0.00338%, amr); Associated with Inborn genetic diseases.

What condition is associated with DYNC2H1 p.Val3137Phe (c.9409G>T)?

DYNC2H1 p.Val3137Phe (c.9409G>T) is associated with Inborn genetic diseases, Jeune syndrome (ClinVar).

How common is DYNC2H1 p.Val3137Phe (c.9409G>T) in the general population?

DYNC2H1 p.Val3137Phe (c.9409G>T) is very rare (popmax 0.00338%, amr) (gnomAD).

What do computational predictors say about DYNC2H1 p.Val3137Phe (c.9409G>T)?

AlphaMissense predicts ambiguous (score 0.3829) — an in-silico prediction, not a clinical call.

DYNC2H1 p.Val3137Phe

c.9409G>T · rs565937214 · VCV1981091

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3829 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00338%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3829	ambiguous
REVEL	0.745	pathogenic-leaning
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 12	GERP 1.3, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 293 kb · p 0.28 · regional, not allelic
Overall
CADD	28.6	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 0.00338% Admixed American · 2/59,210 alleles

Filtering AF 0.00056% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00021%

Overall 0.000311% 5/1,607,344 alleles · very rare exomes 4/1,455,126 · genomes 1/152,218 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00338%	29,605
South Asian	0.00112%	89,482
European (non-Finnish)	0.00017%	588,530

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.Val3137Phe
Coding: c.9409G>T
MANE Select: NM_001377
dbSNP: rs565937214
Type: single nucleotide variant
Location: chr11:103231315 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 3137: 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

Also linked: Jeune syndrome

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-val3137phe (accessed [today's date]).

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