Is DNAH8 p.Pro762= (c.2286G>A) pathogenic?

DNAH8 p.Pro762= (c.2286G>A) is classified Likely benign in DNAH8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-15). Ultra-rare (popmax 0.035%, amr); Associated with primary ciliary dyskinesia.

What condition is associated with DNAH8 p.Pro762= (c.2286G>A)?

DNAH8 p.Pro762= (c.2286G>A) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAH8 p.Pro762= (c.2286G>A) in the general population?

DNAH8 p.Pro762= (c.2286G>A) is ultra-rare (popmax 0.035%, amr) (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.Pro762=

c.2286G>A · rs141715565 · VCV1091322

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.035%, amr)

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 -3.2	GERP -5.7
Overall
CADD	0.118	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.035% Admixed American · 21/59,974 alleles

Filtering AF 0.0234% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0197%

Overall 0.00279% 45/1,613,644 alleles · ultra-rare exomes 33/1,461,486 · genomes 12/152,158 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.035%	2,856
African / African-American	0.0213%	4,685
Middle Eastern	0.0165%	6,060
Remaining individualsnot grpmax-eligible	0.0048%	20,832
East Asian	0.00223%	44,862
South Asian	0.0022%	45,517
European (non-Finnish)	8.48e-05%	1,179,773

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.Pro762=
Coding: c.2286G>A
MANE Select: NM_001206927
dbSNP: rs141715565
Type: single nucleotide variant
Location: chr6:38783030 (GRCh38)
Gene constraint: LOEUF 0.692 · pLI <0.01 (gnomAD)
Residue 762: 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 p.Pro762Leu Uncertain significance ★★ ⚠ 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-pro762 (accessed [today's date]).

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