Is DYNC2H1 p.Val2425Ile (c.7273G>A) pathogenic?

DYNC2H1 p.Val2425Ile (c.7273G>A) is classified Uncertain significance in DYNC2H1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-13). AlphaMissense: likely benign (0.0983); Very rare (popmax 0.00935%, afr); Associated with Inborn genetic diseases.

What condition is associated with DYNC2H1 p.Val2425Ile (c.7273G>A)?

DYNC2H1 p.Val2425Ile (c.7273G>A) is associated with Inborn genetic diseases, Jeune syndrome (ClinVar).

How common is DYNC2H1 p.Val2425Ile (c.7273G>A) in the general population?

DYNC2H1 p.Val2425Ile (c.7273G>A) is very rare (popmax 0.00935%, afr) (gnomAD).

What do computational predictors say about DYNC2H1 p.Val2425Ile (c.7273G>A)?

AlphaMissense predicts likely benign (score 0.0983) — an in-silico prediction, not a clinical call.

DYNC2H1 p.Val2425Ile

c.7273G>A · rs202120495 · VCV2198262

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0983 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00935%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0983	likely benign
REVEL	0.17	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 293 kb · p 0.28 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00935% African / African-American · 7/74,840 alleles

Filtering AF 0.00438% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.0023% 37/1,606,590 alleles · very rare exomes 29/1,454,560 · genomes 8/152,030 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00935%	10,691
European (non-Finnish)	0.00238%	41,991
East Asian	0.00225%	44,508
Admixed American	0.00168%	59,594

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.Val2425Ile
Coding: c.7273G>A
MANE Select: NM_001377
dbSNP: rs202120495
Type: single nucleotide variant
Location: chr11:103188629 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2425: a β-strand; the 'aaa 3' 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-val2425ile (accessed [today's date]).

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