Is CFAP70 p.Trp849Arg (c.2545T>C) pathogenic?

CFAP70 p.Trp849Arg (c.2545T>C) is classified Uncertain significance in CFAP70 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-11). AlphaMissense: likely benign (0.0854); Very rare (popmax 0.00167%, amr).

How common is CFAP70 p.Trp849Arg (c.2545T>C) in the general population?

CFAP70 p.Trp849Arg (c.2545T>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CFAP70 p.Trp849Arg (c.2545T>C)?

AlphaMissense predicts likely benign (score 0.0854) — an in-silico prediction, not a clinical call.

CFAP70 p.Trp849Arg

c.2545T>C · rs1281187576 · VCV2277194

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0854 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0854	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -4.15	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 4.6	GERP 0.84, phastCons 1
Overall
CADD	11.55	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.00167% Admixed American · 1/60,008 alleles

Overall 6.84e-05% 1/1,461,718 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.Trp849Arg
Coding: c.2545T>C
MANE Select: NM_001367801
dbSNP: rs1281187576
Type: single nucleotide variant
Location: chr10:73278242 (GRCh38)
Gene constraint: LOEUF 0.75 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.55
Residue 849: the 'disordered' region; a UniProt-annotated variant site (in)

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.Ala759Glu 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

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-trp849arg (accessed [today's date]).

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