Is CFAP70 p.Ala759Glu (c.2276C>A) pathogenic?

CFAP70 p.Ala759Glu (c.2276C>A) is classified Uncertain significance in CFAP70 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-22). AlphaMissense: likely pathogenic (0.9636); Very rare (popmax 0.0011%, nfe).

How common is CFAP70 p.Ala759Glu (c.2276C>A) in the general population?

CFAP70 p.Ala759Glu (c.2276C>A) is very rare (popmax 0.0011%, nfe) (gnomAD).

What do computational predictors say about CFAP70 p.Ala759Glu (c.2276C>A)?

AlphaMissense predicts likely pathogenic (score 0.9636) — an in-silico prediction, not a clinical call.

CFAP70 p.Ala759Glu

c.2276C>A · VCV3266518

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9636 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9636	likely pathogenic · top 3% in CFAP70
REVEL	0.281	benign-leaning
SaProt	LLR -10.91	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.8, phastCons 1
Overall
CADD	25.9	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 0.0011% European (non-Finnish) · 13/1,180,034 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.000805% 13/1,614,032 alleles · very rare

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: CFAP70
Protein: p.Ala759Glu
Coding: c.2276C>A
MANE Select: NM_001367801
Type: single nucleotide variant
Location: chr10:73291399 (GRCh38)
Gene constraint: LOEUF 0.75 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.55

Full CFAP70 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP70 p.His372Tyr Likely benign ★★ same type
CFAP70 p.Ala433Pro Uncertain significance ★ ⚠ same type
CFAP70 p.Ala78Thr Uncertain significance ★ ⚠ same type
CFAP70 p.Ala7Pro Uncertain significance ★ ⚠ same type
CFAP70 p.Ala948Val Uncertain significance ★ ⚠ same type
CFAP70 p.Ala955Ser Uncertain significance ★ ⚠ same type
CFAP70 p.Arg1045Trp Uncertain significance ★ ⚠ same type
CFAP70 p.Arg1082Gln 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/cfap70-p-ala759glu (accessed [today's date]).

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