Is DYNC2H1 p.Lys265Arg (c.794A>G) pathogenic?

DYNC2H1 p.Lys265Arg (c.794A>G) is classified Uncertain significance in DYNC2H1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-20). AlphaMissense: likely benign (0.0691); Very rare (popmax 6.22e-05%); Associated with Inborn genetic diseases.

What condition is associated with DYNC2H1 p.Lys265Arg (c.794A>G)?

DYNC2H1 p.Lys265Arg (c.794A>G) is associated with Inborn genetic diseases (ClinVar).

How common is DYNC2H1 p.Lys265Arg (c.794A>G) in the general population?

DYNC2H1 p.Lys265Arg (c.794A>G) is very rare (popmax 6.22e-05%) (gnomAD).

What do computational predictors say about DYNC2H1 p.Lys265Arg (c.794A>G)?

AlphaMissense predicts likely benign (score 0.0691) — an in-silico prediction, not a clinical call.

DYNC2H1 p.Lys265Arg

c.794A>G · VCV3506064

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0691 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.22e-05%)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0691	likely benign
REVEL	0.078	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 0.92, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 61 kb · p 0.56 · regional, not allelic
Overall
CADD	16.24	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 6.22e-05%

Overall 6.22e-05% 1/1,606,892 alleles · very rare exomes 0/1,454,748 · genomes 1/152,144 · joint denominator

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.Lys265Arg
Coding: c.794A>G
MANE Select: NM_001377
Type: single nucleotide variant
Location: chr11:103117658 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 265: 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

Similar variants

DYNC2H1 p.Lys265Thr Uncertain significance ★ ⚠ 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-lys265arg (accessed [today's date]).

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