Is DNAH8 p.Ser48Pro (c.142T>C) pathogenic?

DNAH8 p.Ser48Pro (c.142T>C) is classified Uncertain significance in DNAH8 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-08-29). Ultra-rare (popmax 0.0657%, mid); Associated with primary ciliary dyskinesia.

What condition is associated with DNAH8 p.Ser48Pro (c.142T>C)?

DNAH8 p.Ser48Pro (c.142T>C) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAH8 p.Ser48Pro (c.142T>C) in the general population?

DNAH8 p.Ser48Pro (c.142T>C) is ultra-rare (popmax 0.0657%, mid) (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.Ser48Pro

c.142T>C · rs776744908 · VCV525258

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0657%, mid)

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.026	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.7	GERP -3.3
Regional constraint	o/e 1.12	unconstrained · MANE · 19 kb · p 0.008 · regional, not allelic
Overall
CADD	0.083	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0657% Middle Eastern · 4/6,084 alleles

Filtering AF 0.0224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.014%

Overall 0.0138% 222/1,612,558 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0657%	1,521
European (non-Finnish)	0.0166%	6,019
Remaining individualsnot grpmax-eligible	0.016%	6,245
Admixed American	0.00833%	11,999
South Asian	0.00769%	13,010

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.Ser48Pro
Coding: c.142T>C
MANE Select: NM_001206927
dbSNP: rs776744908
Type: single nucleotide variant
Location: chr6:38722951 (GRCh38)
Gene constraint: LOEUF 0.692 · pLI <0.01 (gnomAD)

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-ser48pro (accessed [today's date]).

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