Is DYNC1H1 p.Asp234Glu (c.702T>G) pathogenic?

DYNC1H1 p.Asp234Glu (c.702T>G) is classified Conflicting classifications of pathogenicity in DYNC1H1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-12-19). AlphaMissense: likely benign (0.0847); Ultra-rare (popmax 0.0384%, sas); Associated with Charcot-Marie-Tooth disease.

What condition is associated with DYNC1H1 p.Asp234Glu (c.702T>G)?

DYNC1H1 p.Asp234Glu (c.702T>G) is associated with Charcot-Marie-Tooth disease, Charcot-Marie-Tooth disease axonal type 2O (ClinVar).

How common is DYNC1H1 p.Asp234Glu (c.702T>G) in the general population?

DYNC1H1 p.Asp234Glu (c.702T>G) is ultra-rare (popmax 0.0384%, sas) (gnomAD).

What do computational predictors say about DYNC1H1 p.Asp234Glu (c.702T>G)?

AlphaMissense predicts likely benign (score 0.0847) — an in-silico prediction, not a clinical call.

DYNC1H1 p.Asp234Glu

c.702T>G · rs769311346 · VCV917205

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0847 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0384%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Charcot-Marie-Tooth disease

Computational evidence

Protein change
AlphaMissense	0.0847	likely benign
REVEL	0.171	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.2	GERP -4.6
Regional constraint	o/e 0.51	unconstrained · MANE · 16 kb · p 5.6e-17 · regional, not allelic
Overall
CADD	14.51	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0384% South Asian · 35/91,096 alleles

Filtering AF 0.0283% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0249%

Overall 0.00217% 35/1,614,126 alleles · ultra-rare

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: DYNC1H1
Protein: p.Asp234Glu
Coding: c.702T>G
MANE Select: NM_001376
dbSNP: rs769311346
Type: single nucleotide variant
Location: chr14:101979902 (GRCh38)
Gene constraint: LOEUF 0.117 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Residue 234: the 'stem' region; an α-helix

Full DYNC1H1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Charcot-Marie-Tooth disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Charcot-Marie-Tooth disease axonal type 2O

Similar variants

DYNC1H1 p.Asp234Gly Uncertain significance ★ same residue
DYNC1H1 p.Arg1567Gln Pathogenic/Likely pathogenic ★★ same condition
DYNC1H1 p.Arg1623Gln Pathogenic/Likely pathogenic ★★ same condition
DYNC1H1 p.Arg1962Cys Pathogenic ★★ same condition
DYNC1H1 p.Arg1962His Likely pathogenic ★★ same condition
DYNC1H1 p.Arg2332Cys Pathogenic/Likely pathogenic ★★ same condition
DYNC1H1 p.Arg251Ser Pathogenic/Likely pathogenic ★★ same condition
DYNC1H1 p.Arg264Leu 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/dync1h1-p-asp234glu (accessed [today's date]).

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