Is DYNC2H1 p.Ser2319Arg (c.6957T>G) pathogenic?

DYNC2H1 p.Ser2319Arg (c.6957T>G) is classified Uncertain significance in DYNC2H1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-05-13). AlphaMissense: likely pathogenic (0.9916); Very rare (popmax 0.00134%, afr); Associated with Inborn genetic diseases.

What condition is associated with DYNC2H1 p.Ser2319Arg (c.6957T>G)?

DYNC2H1 p.Ser2319Arg (c.6957T>G) is associated with Inborn genetic diseases (ClinVar).

How common is DYNC2H1 p.Ser2319Arg (c.6957T>G) in the general population?

DYNC2H1 p.Ser2319Arg (c.6957T>G) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about DYNC2H1 p.Ser2319Arg (c.6957T>G)?

AlphaMissense predicts likely pathogenic (score 0.9916) — an in-silico prediction, not a clinical call.

DYNC2H1 p.Ser2319Arg

c.6957T>G · rs1394799972 · VCV2216804

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9916 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9916	likely pathogenic · top 2% in DYNC2H1
REVEL	0.484	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.8	GERP -3.2
Regional constraint	o/e 0.98	unconstrained · MANE · 293 kb · p 0.28 · regional, not allelic
Overall
CADD	16.1	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 0.00134% African / African-American · 1/74,856 alleles

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

Overall 0.000248% 4/1,613,086 alleles · very rare exomes 1/1,461,042 · genomes 3/152,044 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,856
European (non-Finnish)	0.000254%	393,137

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.Ser2319Arg
Coding: c.6957T>G
MANE Select: NM_001377
dbSNP: rs1394799972
Type: single nucleotide variant
Location: chr11:103187403 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2319: the 'aaa 3' region

Full DYNC2H1 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

DYNC2H1 p.Ser2319= Likely benign ★ same residue
DYNC2H1 p.Ala1794Ser Uncertain significance ★★ same condition
DYNC2H1 p.Ala1941Pro Uncertain significance ★★ same condition
DYNC2H1 p.Ala2961Val Uncertain significance ★★ ⚠ same condition
DYNC2H1 p.Ala3172Ser Uncertain significance ★★ same condition
DYNC2H1 p.Ala4003Gly Uncertain significance ★★ ⚠ same condition
DYNC2H1 p.Arg1043Cys Uncertain significance ★★ ⚠ same condition
DYNC2H1 p.Arg1153Gln 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/dync2h1-p-ser2319arg (accessed [today's date]).

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