Is RSPH4A p.Phe644fs (c.1932_1935del) pathogenic?

RSPH4A p.Phe644fs (c.19321935del) is classified Pathogenic in RSPH4A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-17). Absent from gnomAD; Associated with primary ciliary dyskinesia.

What condition is associated with RSPH4A p.Phe644fs (c.1932_1935del)?

RSPH4A p.Phe644fs (c.1932_1935del) is associated with primary ciliary dyskinesia (ClinVar).

How common is RSPH4A p.Phe644fs (c.1932_1935del) in the general population?

RSPH4A p.Phe644fs (c.1932_1935del) is absent from gnomAD (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.Phe644fs

c.1932_1935del · rs2482814588 · VCV2860326

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (6 of 6) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6	GERP 0.61, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: RSPH4A
Protein: p.Phe644fs
Coding: c.1932_1935del
MANE Select: NM_001010892
dbSNP: rs2482814588
Type: Deletion
Location: chr6:116632222 (GRCh38)
Gene constraint: LOEUF 0.816 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.85 · 1 PDB

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 c.1662+2_1662+5del Pathogenic/Likely pathogenic ★★ same condition
RSPH4A c.921+3_921+6del Pathogenic ★★ same condition
RSPH4A p.Gln564fs Pathogenic/Likely pathogenic ★★ same condition
RSPH4A p.Leu592fs Pathogenic ★★ same condition
RSPH4A c.1917-3_1917del Pathogenic ★ same condition
RSPH4A p.Ala416fs Pathogenic ★ same condition
RSPH4A p.Asp578fs Pathogenic ★ same condition
RSPH4A p.Gln155fs 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/rsph4a-p-phe644fs (accessed [today's date]).

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