Is RSPH4A p.Ser93= (c.279T>C) pathogenic?

RSPH4A p.Ser93= (c.279T>C) is classified Likely benign in RSPH4A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2020-08-07). Very rare (popmax 0.00667%, amr); Associated with primary ciliary dyskinesia.

What condition is associated with RSPH4A p.Ser93= (c.279T>C)?

RSPH4A p.Ser93= (c.279T>C) is associated with primary ciliary dyskinesia (ClinVar).

How common is RSPH4A p.Ser93= (c.279T>C) in the general population?

RSPH4A p.Ser93= (c.279T>C) is very rare (popmax 0.00667%, amr) (gnomAD).

How is Primary ciliary dyskinesia inherited?

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

RSPH4A p.Ser93=

c.279T>C · rs755522050 · VCV704949

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00667%, 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 0.046	GERP -3.1
Overall
CADD	6.909	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% Admixed American · 4/60,004 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000434% 7/1,613,984 alleles · very rare exomes 6/1,461,892 · genomes 1/152,092 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	15,001
European (non-Finnish)	0.000254%	393,337

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: RSPH4A
Protein: p.Ser93=
Coding: c.279T>C
MANE Select: NM_001010892
dbSNP: rs755522050
Type: single nucleotide variant
Location: chr6:116616902 (GRCh38)
Gene constraint: LOEUF 0.816 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.85 · 1 PDB
Residue 93: the 'disordered' region

Full RSPH4A 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

RSPH4A p.Arg465Ter Pathogenic ★★ same condition
RSPH4A p.Arg485Ter Pathogenic ★★ same condition
RSPH4A p.Arg490Ter Pathogenic/Likely pathogenic ★★ same condition
RSPH4A p.Arg520Ter Pathogenic ★★ same condition
RSPH4A p.Gln144Ter Pathogenic ★★ same condition
RSPH4A p.Gln154Ter Pathogenic ★★ same condition
RSPH4A p.Gln451Ter Pathogenic ★★ same condition
RSPH4A p.Ala171Pro Uncertain significance ★★ ⚠ 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/rsph4a-p-ser93 (accessed [today's date]).

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