Is DYNC2H1 p.Pro394Thr (c.1180C>A) pathogenic?

DYNC2H1 p.Pro394Thr (c.1180C>A) is classified Uncertain significance in DYNC2H1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-29). AlphaMissense: likely benign (0.1463); Very rare (popmax 0.00111%, sas).

How common is DYNC2H1 p.Pro394Thr (c.1180C>A) in the general population?

DYNC2H1 p.Pro394Thr (c.1180C>A) is very rare (popmax 0.00111%, sas) (gnomAD).

What do computational predictors say about DYNC2H1 p.Pro394Thr (c.1180C>A)?

AlphaMissense predicts likely benign (score 0.1463) — an in-silico prediction, not a clinical call.

DYNC2H1 p.Pro394Thr

c.1180C>A · VCV4913671

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1463 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00111%, sas)

Computational evidence

Protein change
AlphaMissense	0.1463	likely benign
REVEL	0.37	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.2, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 61 kb · p 0.56 · regional, not allelic
Overall
CADD	24.9	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 0.00111% South Asian · 1/90,354 alleles

Overall 6.22e-05% 1/1,606,810 alleles · very rare exomes 1/1,454,820 · genomes 0/151,990 · 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.Pro394Thr
Coding: c.1180C>A
MANE Select: NM_001377
Type: single nucleotide variant
Location: chr11:103120734 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 394: the 'stem' region

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

Similar variants

DYNC2H1 p.Pro394Leu Uncertain significance ★ same residue
DYNC2H1 c.10042+2T>G Pathogenic/Likely pathogenic ★★ same type
DYNC2H1 c.10462-2A>G Likely pathogenic ★★ same type
DYNC2H1 c.10606-14A>G Pathogenic/Likely pathogenic ★★ same type
DYNC2H1 c.10695+1G>A Likely pathogenic ★★ same type
DYNC2H1 c.10813-2A>G Likely pathogenic ★★ same type
DYNC2H1 c.11493+2T>A Likely pathogenic ★★ same type
DYNC2H1 c.11650-1G>A Pathogenic/Likely pathogenic ★★ same type

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-pro394thr (accessed [today's date]).

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