Is DYNC2H1 p.Lys980Arg (c.2939A>G) pathogenic?

DYNC2H1 p.Lys980Arg (c.2939A>G) is classified Uncertain significance in DYNC2H1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-27). AlphaMissense: likely benign (0.1173); Very rare (popmax 0.00236%, eas); Associated with Inborn genetic diseases.

What condition is associated with DYNC2H1 p.Lys980Arg (c.2939A>G)?

DYNC2H1 p.Lys980Arg (c.2939A>G) is associated with Inborn genetic diseases, Jeune syndrome (ClinVar).

How common is DYNC2H1 p.Lys980Arg (c.2939A>G) in the general population?

DYNC2H1 p.Lys980Arg (c.2939A>G) is very rare (popmax 0.00236%, eas) (gnomAD).

What do computational predictors say about DYNC2H1 p.Lys980Arg (c.2939A>G)?

AlphaMissense predicts likely benign (score 0.1173) — an in-silico prediction, not a clinical call.

DYNC2H1 p.Lys980Arg

c.2939A>G · rs144066746 · VCV1716956

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1173 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00236%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1173	likely benign
REVEL	0.037	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 7	GERP 1.4, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 61 kb · p 0.56 · regional, not allelic
Overall
CADD	21.6	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 0.00236% East Asian · 1/42,284 alleles

Filtering AF 6.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000256% 4/1,564,212 alleles · very rare exomes 3/1,411,872 · genomes 1/152,340 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00236%	42,284
European (non-Finnish)	0.00026%	384,686

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.Lys980Arg
Coding: c.2939A>G
MANE Select: NM_001377
dbSNP: rs144066746
Type: single nucleotide variant
Location: chr11:103148610 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 980: the 'stem' 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 p.Lys980Asn Uncertain significance ★★ ⚠ same residue
DYNC2H1 p.Lys980= Likely benign ★ same residue
DYNC2H1 p.Lys980Glu Uncertain significance ★ ⚠ 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

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-lys980arg (accessed [today's date]).

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