Is DYNC1H1 p.Pro2256His (c.6767C>A) pathogenic?

DYNC1H1 p.Pro2256His (c.6767C>A) is classified Uncertain significance in DYNC1H1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-12-01). AlphaMissense: likely pathogenic (0.9971); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DYNC1H1 p.Pro2256His (c.6767C>A)?

DYNC1H1 p.Pro2256His (c.6767C>A) is associated with Inborn genetic diseases (ClinVar).

How common is DYNC1H1 p.Pro2256His (c.6767C>A) in the general population?

DYNC1H1 p.Pro2256His (c.6767C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DYNC1H1 p.Pro2256His (c.6767C>A)?

AlphaMissense predicts likely pathogenic (score 0.9971) — an in-silico prediction, not a clinical call.

DYNC1H1 p.Pro2256His

c.6767C>A · rs2503756742 · VCV1755320

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9971 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9971	likely pathogenic · top 8% in DYNC1H1
REVEL	0.93	moderately pathogenic-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this damaging; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.5, phastCons 1
Regional constraint	o/e 0.30	constrained · MANE · 3,245 bp · p 4.2e-21 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DYNC1H1
Protein: p.Pro2256His
Coding: c.6767C>A
MANE Select: NM_001376
dbSNP: rs2503756742
Type: single nucleotide variant
Location: chr14:102012023 (GRCh38)
Gene constraint: LOEUF 0.117 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Residue 2256: an α-helix; the 'aaa 2' region

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-pro2256his (accessed [today's date]).

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