Is CFAP69 p.Pro459Leu (c.1376C>T) pathogenic?

CFAP69 p.Pro459Leu (c.1376C>T) is classified Benign in CFAP69 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). AlphaMissense: likely benign (0.0858); Low-frequency (popmax 2.9%, afr).

How common is CFAP69 p.Pro459Leu (c.1376C>T) in the general population?

CFAP69 p.Pro459Leu (c.1376C>T) is low-frequency (popmax 2.9%, afr) (gnomAD).

What do computational predictors say about CFAP69 p.Pro459Leu (c.1376C>T)?

AlphaMissense predicts likely benign (score 0.0858) — an in-silico prediction, not a clinical call.

CFAP69 p.Pro459Leu

c.1376C>T · rs17865959 · VCV776236

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0858 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.9%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0858	likely benign
REVEL	0.075	moderately benign-leaning
SaProt	LLR -7.70	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.44	GERP 2
Regional constraint	o/e 0.97	unconstrained · MANE · 65 kb · p 0.37 · regional, not allelic
Overall
CADD	18.27	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.9% African / African-American · 2,011/69,242 alleles

Filtering AF 2.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.76%

Overall 0.152% 2,232/1,469,046 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.9%	34
Admixed American	0.183%	548
Remaining individualsnot grpmax-eligible	0.182%	550
South Asian	0.0185%	5,397
Middle Eastern	0.0181%	5,530
East Asian	0.0128%	7,815
European (non-Finnish)	0.00235%	42,601

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.Pro459Leu
Coding: c.1376C>T
MANE Select: NM_001039706
dbSNP: rs17865959
Type: single nucleotide variant
Location: chr7:90282895 (GRCh38)
Gene constraint: LOEUF 1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.48
Residue 459: a UniProt-annotated variant site (in spgf24); a UniProt-annotated variant site (in)

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

Similar variants

CFAP69 p.Pro459= Likely benign ★ same residue
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

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-pro459leu (accessed [today's date]).

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