Is CFAP65 p.Glu1840Ter (c.5518G>T) pathogenic?

CFAP65 p.Glu1840Ter (c.5518G>T) is classified Likely pathogenic in CFAP65 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-22). Very rare (popmax 0.00167%, amr); Associated with Susceptibility to severe COVID-19.

What condition is associated with CFAP65 p.Glu1840Ter (c.5518G>T)?

CFAP65 p.Glu1840Ter (c.5518G>T) is associated with Susceptibility to severe COVID-19 (ClinVar).

How common is CFAP65 p.Glu1840Ter (c.5518G>T) in the general population?

CFAP65 p.Glu1840Ter (c.5518G>T) is very rare (popmax 0.00167%, amr) (gnomAD).

CFAP65 p.Glu1840Ter

c.5518G>T · VCV3256948

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

Susceptibility to severe COVID-19

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 33 of 35
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP 1.5, phastCons 1
Overall
CADD	40.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,026 alleles

Overall 6.84e-05% 1/1,461,704 alleles · very rare

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: CFAP65
Protein: p.Glu1840Ter
Coding: c.5518G>T
MANE Select: NM_194302
Type: single nucleotide variant
Location: chr2:219003989 (GRCh38)
Gene constraint: LOEUF 0.85 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.03
Residue 1840: a UniProt-annotated variant site (in spgf40)

Full CFAP65 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Susceptibility to severe COVID-19

Similar variants

CFAP65 p.Trp1201Ter Likely pathogenic ★ same condition
CFAP65 p.Phe1718Cys Likely benign same condition
CFAP65 p.Arg1231= Benign ★★ same type
CFAP65 p.Arg1545Gln Benign ★★ same type
CFAP65 p.Arg760Gln Benign ★★ same type
CFAP65 p.Asp1313= Likely benign ★★ same type
CFAP65 p.Leu1127= Benign/Likely benign ★★ same type
CFAP65 p.Leu1523= Benign/Likely benign ★★ same type

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/cfap65-p-glu1840ter (accessed [today's date]).

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