Is DYNC1H1 p.Pro340Ser (c.1018C>T) pathogenic?

DYNC1H1 p.Pro340Ser (c.1018C>T) is classified Uncertain significance in DYNC1H1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-24). AlphaMissense: likely pathogenic (0.9919); Very rare (popmax 6.2e-05%).

How common is DYNC1H1 p.Pro340Ser (c.1018C>T) in the general population?

DYNC1H1 p.Pro340Ser (c.1018C>T) is very rare (popmax 6.2e-05%) (gnomAD).

What do computational predictors say about DYNC1H1 p.Pro340Ser (c.1018C>T)?

AlphaMissense predicts likely pathogenic (score 0.9919) — an in-silico prediction, not a clinical call.

DYNC1H1 p.Pro340Ser

c.1018C>T · rs752337814 · VCV2577763

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9919 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Computational evidence

Protein change
AlphaMissense	0.9919	likely pathogenic
REVEL	0.558	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.43	unconstrained · MANE · 3,602 bp · p 2.9e-46 · regional, not allelic
Overall
CADD	24.4	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 6.2e-05%

Overall 6.2e-05% 1/1,614,122 alleles · very rare exomes 1/1,461,882 · genomes 0/152,240 · 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: DYNC1H1
Protein: p.Pro340Ser
Coding: c.1018C>T
MANE Select: NM_001376
dbSNP: rs752337814
Type: single nucleotide variant
Location: chr14:101983075 (GRCh38)
Gene constraint: LOEUF 0.117 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Residue 340: the 'stem' region

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

Similar variants

DYNC1H1 p.Pro340= 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-pro340ser (accessed [today's date]).

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