Is DNAH8 p.Ser2108Ter (c.6323C>A) pathogenic?

DNAH8 p.Ser2108Ter (c.6323C>A) is classified Pathogenic in DNAH8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-18). Very rare (popmax 8.51e-05%, nfe); Associated with primary ciliary dyskinesia.

What condition is associated with DNAH8 p.Ser2108Ter (c.6323C>A)?

DNAH8 p.Ser2108Ter (c.6323C>A) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAH8 p.Ser2108Ter (c.6323C>A) in the general population?

DNAH8 p.Ser2108Ter (c.6323C>A) is very rare (popmax 8.51e-05%, nfe) (gnomAD).

How is Primary ciliary dyskinesia inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

DNAH8 p.Ser2108Ter

c.6323C>A · VCV4733574

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.51e-05%, nfe)

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 45 of 93
Splicing
SpliceAI	Δ0.55	acceptor loss, 12 bp away · masked 0 · deltas
Pangolin	Δ0.51	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.7	GERP 2.6, phastCons 1
Overall
CADD	46.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.51e-05% European (non-Finnish) · 1/1,175,440 alleles

Overall 6.93e-05% 1/1,442,996 alleles · very rare

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: DNAH8
Protein: p.Ser2108Ter
Coding: c.6323C>A
MANE Select: NM_001206927
Type: single nucleotide variant
Location: chr6:38863885 (GRCh38)
Gene constraint: LOEUF 0.692 · pLI <0.01 (gnomAD)
Residue 2108: a UniProt-annotated variant site (found in a patient with primary ciliary dyskinesia; uncertain significance); the 'aaa 2' region

Full DNAH8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

primary ciliary dyskinesia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Primary ciliary dyskinesia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Neonatal
Prevalence: 1-5 / 10 000 (Pakistan)

Similar variants

DNAH8 p.Ser2108= Likely benign ★ same residue
DNAH8 c.10963-1G>A Likely pathogenic ★★ same condition
DNAH8 c.11563+1G>T Likely pathogenic ★★ same condition
DNAH8 c.2664+2T>C Likely pathogenic ★★ same condition
DNAH8 c.5734-1G>T Likely pathogenic ★★ same condition
DNAH8 p.Arg1090Ter Pathogenic/Likely pathogenic ★★ same condition
DNAH8 p.Arg207Ter Pathogenic/Likely pathogenic ★★ same condition
DNAH8 p.Arg2878Ter 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/dnah8-p-ser2108ter (accessed [today's date]).

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