Is DYNC2H1 p.Ala2012Val (c.6035C>T) pathogenic?

DYNC2H1 p.Ala2012Val (c.6035C>T) is classified Likely pathogenic in DYNC2H1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-17). AlphaMissense: likely pathogenic (0.8606); Very rare (popmax 0.000254%, nfe); Associated with asphyxiating thoracic dystrophy 3.

What condition is associated with DYNC2H1 p.Ala2012Val (c.6035C>T)?

DYNC2H1 p.Ala2012Val (c.6035C>T) is associated with asphyxiating thoracic dystrophy 3 (ClinVar).

How common is DYNC2H1 p.Ala2012Val (c.6035C>T) in the general population?

DYNC2H1 p.Ala2012Val (c.6035C>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about DYNC2H1 p.Ala2012Val (c.6035C>T)?

AlphaMissense predicts likely pathogenic (score 0.8606) — an in-silico prediction, not a clinical call.

DYNC2H1 p.Ala2012Val

c.6035C>T · rs1215030552 · VCV3064165

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8606 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

asphyxiating thoracic dystrophy 3

Computational evidence

Protein change
AlphaMissense	0.8606	likely pathogenic ✓ concordant with ClinVar
REVEL	0.89	moderately pathogenic-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this damaging; SaProt makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.38 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 8,693 bp · p 6.7e-06 · regional, not allelic
Overall
CADD	28.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,688 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,613,488 alleles · very rare exomes 3/1,461,326 · genomes 0/152,162 · 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.Ala2012Val
Coding: c.6035C>T
MANE Select: NM_001377
dbSNP: rs1215030552
Type: single nucleotide variant
Location: chr11:103177716 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2012: a turn; the 'aaa 2' region

Full DYNC2H1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

asphyxiating thoracic dystrophy 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DYNC2H1 p.Ala2012Thr Uncertain significance ★ ⚠ same residue
DYNC2H1 c.10042+2T>G Pathogenic/Likely pathogenic ★★ same condition
DYNC2H1 c.10462-2A>G Likely pathogenic ★★ same condition
DYNC2H1 c.10606-14A>G Pathogenic/Likely pathogenic ★★ same condition
DYNC2H1 c.12156+1G>A Pathogenic/Likely pathogenic ★★ same condition
DYNC2H1 c.12457-1G>C Likely pathogenic ★★ same condition
DYNC2H1 c.1662-2A>G Likely pathogenic ★★ same condition
DYNC2H1 c.2106+2T>C 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/dync2h1-p-ala2012val (accessed [today's date]).

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