Is DYNC1H1 p.Ala54Val (c.161C>T) pathogenic?

DYNC1H1 p.Ala54Val (c.161C>T) is classified Conflicting classifications of pathogenicity in DYNC1H1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-10-26). AlphaMissense: likely benign (0.0779); Very rare (popmax 0.00648%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DYNC1H1 p.Ala54Val (c.161C>T)?

DYNC1H1 p.Ala54Val (c.161C>T) is associated with Inborn genetic diseases, Charcot-Marie-Tooth disease axonal type 2O, autosomal dominant cerebellar ataxia (ClinVar).

How common is DYNC1H1 p.Ala54Val (c.161C>T) in the general population?

DYNC1H1 p.Ala54Val (c.161C>T) is very rare (popmax 0.00648%, nfe) (gnomAD).

What do computational predictors say about DYNC1H1 p.Ala54Val (c.161C>T)?

AlphaMissense predicts likely benign (score 0.0779) — an in-silico prediction, not a clinical call.

DYNC1H1 p.Ala54Val

c.161C>T · rs772070566 · VCV312616

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0779 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00648%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0779	likely benign
REVEL	0.05	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 7.1	GERP 1.7, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 225 bp · p 0.67 · regional, not allelic
Overall
CADD	24.5	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 0.00648% European (non-Finnish) · 76/1,173,296 alleles

Filtering AF 0.0053% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00484%

Overall 0.00488% 78/1,598,042 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00648%	15,438
Remaining individualsnot grpmax-eligible	0.00162%	61,788
African / African-American	0.00134%	74,724

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.Ala54Val
Coding: c.161C>T
MANE Select: NM_001376
dbSNP: rs772070566
Type: single nucleotide variant
Location: chr14:101964852 (GRCh38)
Gene constraint: LOEUF 0.117 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Residue 54: 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 autosomal dominant cerebellar ataxia

Similar variants

DYNC1H1 p.Ala54Ser Uncertain significance ★ ⚠ same residue
DYNC1H1 p.Ala54= Likely benign ★ same residue
DYNC1H1 p.Ala54Glu 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

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-ala54val (accessed [today's date]).

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