Is CFAP69 p.Leu421= (c.1261C>T) pathogenic?

CFAP69 p.Leu421= (c.1261C>T) is classified Likely benign in CFAP69 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-01). Rare (popmax 0.579%, nfe).

How common is CFAP69 p.Leu421= (c.1261C>T) in the general population?

CFAP69 p.Leu421= (c.1261C>T) is rare (popmax 0.579%, nfe) (gnomAD).

CFAP69 p.Leu421=

c.1261C>T · VCV3387981

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.579%, nfe)

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 1.8	GERP 2.6, phastCons 0.94
Overall
CADD	9.209	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.579% European (non-Finnish) · 6,834/1,179,732 alleles

Filtering AF 0.568% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.563%

Overall 0.567% 9,151/1,613,246 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	2.57%	39
Ashkenazi Jewishnot grpmax-eligible	0.804%	124
European (non-Finnish)grpmax	0.579%	173
Remaining individualsnot grpmax-eligible	0.488%	205
Admixed American	0.0971%	1,030
African / African-American	0.0827%	1,210
Middle Eastern	0.0825%	1,212
South Asian	0.0033%	30,317

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CFAP69
Protein: p.Leu421=
Coding: c.1261C>T
MANE Select: NM_001039706
Type: single nucleotide variant
Location: chr7:90279782 (GRCh38)
Gene constraint: LOEUF 1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.48
Residue 421: a UniProt-annotated variant site (in spgf24)

Full CFAP69 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP69 p.Phe731Leu Uncertain significance ★★ ⚠ same type
CFAP69 p.Tyr819His Uncertain significance ★★ ⚠ same type
CFAP69 c.1857+47T>A Benign ★★ same type
CFAP69 c.682+50A>C Benign ★★ same type
CFAP69 p.Ala12= Benign ★★ same type
CFAP69 p.Ala182= Benign ★★ same type
CFAP69 p.Ala8= Benign/Likely benign ★★ same type
CFAP69 p.Arg106His 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/cfap69-p-leu421 (accessed [today's date]).

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