Is DYNC1H1 p.Ile153Val (c.457A>G) pathogenic?

DYNC1H1 p.Ile153Val (c.457A>G) is classified Likely benign in DYNC1H1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-10). AlphaMissense: likely benign (0.1086); Ultra-rare (popmax 0.0717%, amr); Associated with Inborn genetic diseases.

What condition is associated with DYNC1H1 p.Ile153Val (c.457A>G)?

DYNC1H1 p.Ile153Val (c.457A>G) is associated with Inborn genetic diseases, Charcot-Marie-Tooth disease axonal type 2O (ClinVar).

How common is DYNC1H1 p.Ile153Val (c.457A>G) in the general population?

DYNC1H1 p.Ile153Val (c.457A>G) is ultra-rare (popmax 0.0717%, amr) (gnomAD).

What do computational predictors say about DYNC1H1 p.Ile153Val (c.457A>G)?

AlphaMissense predicts likely benign (score 0.1086) — an in-silico prediction, not a clinical call.

DYNC1H1 p.Ile153Val

c.457A>G · rs140905741 · VCV472536

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1086 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0717%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1086	likely benign
REVEL	0.196	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 9.2	GERP 2.7, phastCons 1
Regional constraint	o/e 0.51	unconstrained · MANE · 16 kb · p 5.6e-17 · regional, not allelic
Overall
CADD	20.4	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 0.0717% Admixed American · 43/60,000 alleles

Filtering AF 0.0546% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0486%

Overall 0.0102% 164/1,614,072 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0717%	1,395
Remaining individualsnot grpmax-eligible	0.0208%	4,807
European (non-Finnish)	0.00864%	11,569
African / African-American	0.00667%	14,983
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606

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.Ile153Val
Coding: c.457A>G
MANE Select: NM_001376
dbSNP: rs140905741
Type: single nucleotide variant
Location: chr14:101979431 (GRCh38)
Gene constraint: LOEUF 0.117 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Residue 153: the 'stem' region; an α-helix

Full DYNC1H1 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: Charcot-Marie-Tooth disease axonal type 2O

Similar variants

DYNC1H1 p.Ile153Leu Likely benign ★ 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-ile153val (accessed [today's date]).

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