Is DYNC1H1 p.Ser2607= (c.7821C>T) pathogenic?

DYNC1H1 p.Ser2607= (c.7821C>T) is classified Conflicting classifications of pathogenicity in DYNC1H1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-11-15). Ultra-rare (popmax 0.033%, mid); Associated with autosomal dominant cerebellar ataxia.

What condition is associated with DYNC1H1 p.Ser2607= (c.7821C>T)?

DYNC1H1 p.Ser2607= (c.7821C>T) is associated with autosomal dominant cerebellar ataxia, Charcot-Marie-Tooth disease axonal type 2O (ClinVar).

How common is DYNC1H1 p.Ser2607= (c.7821C>T) in the general population?

DYNC1H1 p.Ser2607= (c.7821C>T) is ultra-rare (popmax 0.033%, mid) (gnomAD).

DYNC1H1 p.Ser2607=

c.7821C>T · rs375547282 · VCV883957

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Conditions

autosomal dominant cerebellar ataxia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -13	GERP -5
Overall
CADD	5.221	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.0101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00811%

Overall 0.0031% 50/1,614,254 alleles · ultra-rare exomes 44/1,461,872 · genomes 6/152,382 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,031
South Asian	0.0165%	6,073
Remaining individualsnot grpmax-eligible	0.008%	12,502
East Asian	0.00668%	14,965
African / African-American	0.00266%	37,537
European (non-Finnish)	0.00195%	51,306

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.Ser2607=
Coding: c.7821C>T
MANE Select: NM_001376
dbSNP: rs375547282
Type: single nucleotide variant
Location: chr14:102016972 (GRCh38)
Gene constraint: LOEUF 0.117 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Residue 2607: an α-helix; the 'aaa 3' region

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

Disease context

autosomal dominant cerebellar ataxia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Charcot-Marie-Tooth disease axonal type 2O

Similar variants

DYNC1H1 p.Ser2607Gly Uncertain significance ★ same residue
DYNC1H1 p.Arg1567Gln Pathogenic/Likely pathogenic ★★ same condition
DYNC1H1 p.Arg1623Gln Pathogenic/Likely pathogenic ★★ same condition
DYNC1H1 p.Arg1962Cys Pathogenic ★★ same condition
DYNC1H1 p.Arg1962His Likely pathogenic ★★ same condition
DYNC1H1 p.Arg2332Cys Pathogenic/Likely pathogenic ★★ same condition
DYNC1H1 p.Arg251Ser Pathogenic/Likely pathogenic ★★ same condition
DYNC1H1 p.Arg264Leu Pathogenic ★★ 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-ser2607 (accessed [today's date]).

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