Is DYNC1H1 p.Val18Ala (c.53T>C) pathogenic?

DYNC1H1 p.Val18Ala (c.53T>C) is classified Uncertain significance in DYNC1H1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-10-31). AlphaMissense: likely benign (0.133); Very rare (popmax 0.00034%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DYNC1H1 p.Val18Ala (c.53T>C)?

DYNC1H1 p.Val18Ala (c.53T>C) is associated with Inborn genetic diseases (ClinVar).

How common is DYNC1H1 p.Val18Ala (c.53T>C) in the general population?

DYNC1H1 p.Val18Ala (c.53T>C) is very rare (popmax 0.00034%, nfe) (gnomAD).

What do computational predictors say about DYNC1H1 p.Val18Ala (c.53T>C)?

AlphaMissense predicts likely benign (score 0.133) — an in-silico prediction, not a clinical call.

DYNC1H1 p.Val18Ala

c.53T>C · rs1566991030 · VCV1747308

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.133 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00034%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.133	likely benign
REVEL	0.09	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 7.3	GERP 1.7, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 225 bp · p 0.67 · regional, not allelic
Overall
CADD	23.8	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 0.00034% European (non-Finnish) · 4/1,175,516 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000277% 4/1,444,912 alleles · very 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.Val18Ala
Coding: c.53T>C
MANE Select: NM_001376
dbSNP: rs1566991030
Type: single nucleotide variant
Location: chr14:101964744 (GRCh38)
Gene constraint: LOEUF 0.117 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)

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

Similar variants

DYNC1H1 p.Arg1567Gln Pathogenic/Likely pathogenic ★★ same condition
DYNC1H1 p.Arg1962His Likely pathogenic ★★ same condition
DYNC1H1 p.Arg292Trp Pathogenic ★★ same condition
DYNC1H1 p.Gly2330Glu Pathogenic/Likely pathogenic ★★ same condition
DYNC1H1 p.Phe1093Ser Pathogenic ★★ same condition
DYNC1H1 c.3444+3G>A Uncertain significance ★★ same condition
DYNC1H1 c.4074+5A>G Uncertain significance ★★ same condition
DYNC1H1 c.6618+5C>T 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/dync1h1-p-val18ala (accessed [today's date]).

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