Is DYNC1H1 p.Arg751Gln (c.2252G>A) pathogenic?

DYNC1H1 p.Arg751Gln (c.2252G>A) is classified Conflicting classifications of pathogenicity in DYNC1H1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-11-04). AlphaMissense: likely pathogenic (0.9872); Absent from gnomAD v4.1.

How common is DYNC1H1 p.Arg751Gln (c.2252G>A) in the general population?

DYNC1H1 p.Arg751Gln (c.2252G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DYNC1H1 p.Arg751Gln (c.2252G>A)?

AlphaMissense predicts likely pathogenic (score 0.9872) — an in-silico prediction, not a clinical call.

DYNC1H1 p.Arg751Gln

c.2252G>A · rs2141275001 · VCV1342055

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9872 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.9872	likely pathogenic
REVEL	0.629	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.43	unconstrained · MANE · 3,602 bp · p 2.9e-46 · regional, not allelic
Overall
CADD	31.0	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

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.Arg751Gln
Coding: c.2252G>A
MANE Select: NM_001376
dbSNP: rs2141275001
Type: single nucleotide variant
Location: chr14:101986477 (GRCh38)
Gene constraint: LOEUF 0.117 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Residue 751: an α-helix; the 'stem' region; the 'interaction with dync1li2' region

Full DYNC1H1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DYNC1H1 p.Arg751= Likely benign ★ same residue
DYNC1H1 c.4396-1G>C Likely pathogenic ★★ same type
DYNC1H1 p.Ala4519Val Likely pathogenic ★★ same type
DYNC1H1 p.Arg1567Gln Pathogenic/Likely pathogenic ★★ same type
DYNC1H1 p.Arg1623Gln Pathogenic/Likely pathogenic ★★ same type
DYNC1H1 p.Arg1623Trp Pathogenic ★★ same type
DYNC1H1 p.Arg1962Cys Pathogenic ★★ same type
DYNC1H1 p.Arg1962His 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/dync1h1-p-arg751gln (accessed [today's date]).

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