Is CFAP46 p.Ser2666= (c.7998T>C) pathogenic?

CFAP46 p.Ser2666= (c.7998T>C) is classified Likely benign in CFAP46 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-01). Very rare (popmax 0.00167%, amr).

How common is CFAP46 p.Ser2666= (c.7998T>C) in the general population?

CFAP46 p.Ser2666= (c.7998T>C) is very rare (popmax 0.00167%, amr) (gnomAD).

CFAP46 p.Ser2666=

c.7998T>C · rs781522715 · VCV2640979

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

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 -0.43	GERP -0.82
Overall
CADD	1.309	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,992 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,612,742 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,992
European (non-Finnish)	0.00017%	589,943

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: CFAP46
Protein: p.Ser2666=
Coding: c.7998T>C
MANE Select: NM_001200049
dbSNP: rs781522715
Type: single nucleotide variant
Location: chr10:132808571 (GRCh38)
Gene constraint: LOEUF 0.888 · pLI <0.01 (gnomAD)

Full CFAP46 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP46 p.Ala1708Val Uncertain significance ★ ⚠ same type
CFAP46 p.Ala1742Glu Uncertain significance ★ ⚠ same type
CFAP46 p.Ala1742Val Uncertain significance ★ ⚠ same type
CFAP46 p.Ala1746Glu Uncertain significance ★ ⚠ same type
CFAP46 p.Ala1788Val Uncertain significance ★ ⚠ same type
CFAP46 p.Ala1806Val Uncertain significance ★ ⚠ same type
CFAP46 p.Ala1811Val Uncertain significance ★ ⚠ same type
CFAP46 p.Ala1871Val Uncertain significance ★ ⚠ 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/cfap46-p-ser2666 (accessed [today's date]).

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