Is CFAP69 p.Glu607Asp (c.1821A>T) pathogenic?

CFAP69 p.Glu607Asp (c.1821A>T) is classified Uncertain significance in CFAP69 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-25). AlphaMissense: likely pathogenic (0.6692); Very rare (popmax 0.00205%, nfe).

How common is CFAP69 p.Glu607Asp (c.1821A>T) in the general population?

CFAP69 p.Glu607Asp (c.1821A>T) is very rare (popmax 0.00205%, nfe) (gnomAD).

What do computational predictors say about CFAP69 p.Glu607Asp (c.1821A>T)?

AlphaMissense predicts likely pathogenic (score 0.6692) — an in-silico prediction, not a clinical call.

CFAP69 p.Glu607Asp

c.1821A>T · rs751763775 · VCV2489083

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6692 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00205%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6692	likely pathogenic
REVEL	0.231	benign-leaning
SaProt	LLR -7.78	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP 3.2, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 65 kb · p 0.37 · regional, not allelic
Overall
CADD	23.0	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 0.00205% European (non-Finnish) · 24/1,168,188 alleles

Filtering AF 0.00139% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00117%

Overall 0.00159% 25/1,574,238 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00205%	48,675
Finnishnot grpmax-eligible	0.00157%	63,552

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.Glu607Asp
Coding: c.1821A>T
MANE Select: NM_001039706
dbSNP: rs751763775
Type: single nucleotide variant
Location: chr7:90297794 (GRCh38)
Gene constraint: LOEUF 1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.48
Residue 607: 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.Glu607Gly Uncertain significance ★ ⚠ 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-glu607asp (accessed [today's date]).

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