Is DNAH8 p.Asp640= (c.1920C>T) pathogenic?

DNAH8 p.Asp640= (c.1920C>T) is classified Benign in DNAH8 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-01). Common (popmax 7.2%, afr) — too common for a highly-penetrant pathogenic allele; Associated with primary ciliary dyskinesia.

What condition is associated with DNAH8 p.Asp640= (c.1920C>T)?

DNAH8 p.Asp640= (c.1920C>T) is associated with primary ciliary dyskinesia (ClinVar).

How is Primary ciliary dyskinesia inherited?

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

DNAH8 p.Asp640=

Q: How common is DNAH8 p.Asp640= (c.1920C>T) in the general population?

DNAH8 p.Asp640= (c.1920C>T) is common (popmax 7.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1920C>T · rs78139815 · VCV414410

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 7.2%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

primary ciliary dyskinesia

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 -1.2	GERP -5.5
Overall
CADD	2.15	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.2% African / African-American · 5,391/74,902 alleles

Filtering AF 7.04% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.97%

Overall 0.395% 6,367/1,612,848 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.2%	14
Admixed American	0.615%	163
Remaining individualsnot grpmax-eligible	0.504%	198
Middle Eastern	0.496%	202
European (non-Finnish)	0.0215%	4,661
South Asian	0.00879%	11,381
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,566

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.Asp640=
Coding: c.1920C>T
MANE Select: NM_001206927
dbSNP: rs78139815
Type: single nucleotide variant
Location: chr6:38775909 (GRCh38)
Gene constraint: LOEUF 0.692 · pLI <0.01 (gnomAD)
Residue 640: a UniProt-annotated variant site (found in a patient with primary ciliary dyskinesia; uncertain significance)

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 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
DNAH8 p.Arg4166Ter Pathogenic/Likely 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-asp640 (accessed [today's date]).

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