Is CFAP100 p.Arg566Pro (c.1697G>C) pathogenic?

CFAP100 p.Arg566Pro (c.1697G>C) is classified Uncertain significance in CFAP100 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-26). AlphaMissense: likely pathogenic (0.8441); Very rare (popmax 0.00224%, eas).

How common is CFAP100 p.Arg566Pro (c.1697G>C) in the general population?

CFAP100 p.Arg566Pro (c.1697G>C) is very rare (popmax 0.00224%, eas) (gnomAD).

What do computational predictors say about CFAP100 p.Arg566Pro (c.1697G>C)?

AlphaMissense predicts likely pathogenic (score 0.8441) — an in-silico prediction, not a clinical call.

CFAP100 p.Arg566Pro

c.1697G>C · rs142534437 · VCV3143296

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8441 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8441	likely pathogenic · top 3% in CFAP100
REVEL	0.381	indeterminate
SaProt	LLR -14.09	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 12	GERP 1.8, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 40 kb · p 0.22 · regional, not allelic
Overall
CADD	25.2	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

Grpmax group 0.00224% East Asian · 1/44,738 alleles

Overall 0.000124% 2/1,612,042 alleles · very rare exomes 2/1,459,902 · genomes 0/152,140 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00224%	44,738
European (non-Finnish)	8.48e-05%	1,178,598

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: CFAP100
Protein: p.Arg566Pro
Coding: c.1697G>C
MANE Select: NM_182628
dbSNP: rs142534437
Type: single nucleotide variant
Location: chr3:126435627 (GRCh38)
Gene constraint: LOEUF 1.041 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.85 · 1 PDB
Residue 566: the 'interaction with ttll13' region

Full CFAP100 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP100 p.Arg566Cys Uncertain significance ★ ⚠ same residue
CFAP100 p.Arg566His Uncertain significance ★ ⚠ same residue
CFAP100 p.Ala126Ser Uncertain significance ★ ⚠ same type
CFAP100 p.Ala179Val Uncertain significance ★ ⚠ same type
CFAP100 p.Ala224Asp Uncertain significance ★ ⚠ same type
CFAP100 p.Ala499Thr Uncertain significance ★ ⚠ same type
CFAP100 p.Ala563Val Uncertain significance ★ ⚠ same type
CFAP100 p.Ala565Val 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/cfap100-p-arg566pro (accessed [today's date]).

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