Is CFAP69 p.Leu144Pro (c.431T>C) pathogenic?

CFAP69 p.Leu144Pro (c.431T>C) is classified Uncertain significance in CFAP69 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-25). AlphaMissense: likely pathogenic (0.8555); Absent from gnomAD v4.1.

How common is CFAP69 p.Leu144Pro (c.431T>C) in the general population?

CFAP69 p.Leu144Pro (c.431T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CFAP69 p.Leu144Pro (c.431T>C)?

AlphaMissense predicts likely pathogenic (score 0.8555) — an in-silico prediction, not a clinical call.

CFAP69 p.Leu144Pro

c.431T>C · VCV3832407

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8555 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8555	likely pathogenic · top 6% in CFAP69
REVEL	0.576	indeterminate
SaProt	LLR -17.15	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 4.2, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 65 kb · p 0.37 · regional, not allelic
Overall
CADD	29.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CFAP69
Protein: p.Leu144Pro
Coding: c.431T>C
MANE Select: NM_001039706
Type: single nucleotide variant
Location: chr7:90265375 (GRCh38)
Gene constraint: LOEUF 1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.48

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-leu144pro (accessed [today's date]).

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