Is CFAP206 p.Pro220Leu (c.659C>T) pathogenic?

CFAP206 p.Pro220Leu (c.659C>T) is classified Uncertain significance in CFAP206 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-10). AlphaMissense: likely benign (0.2566); Very rare (popmax 0.00458%, nfe).

How common is CFAP206 p.Pro220Leu (c.659C>T) in the general population?

CFAP206 p.Pro220Leu (c.659C>T) is very rare (popmax 0.00458%, nfe) (gnomAD).

What do computational predictors say about CFAP206 p.Pro220Leu (c.659C>T)?

AlphaMissense predicts likely benign (score 0.2566) — an in-silico prediction, not a clinical call.

CFAP206 p.Pro220Leu

c.659C>T · rs267601153 · VCV2475103

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2566 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00458%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2566	likely benign
REVEL	0.307	indeterminate
SaProt	LLR -10.32	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 0.81, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 54 kb · p 0.001 · regional, not allelic
Overall
CADD	23.6	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 0.00458% European (non-Finnish) · 54/1,180,058 alleles

Filtering AF 0.00358% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00321%

Overall 0.00335% 54/1,614,062 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: CFAP206
Protein: p.Pro220Leu
Coding: c.659C>T
MANE Select: NM_001031743
dbSNP: rs267601153
Type: single nucleotide variant
Location: chr6:87418235 (GRCh38)
Gene constraint: LOEUF 0.992 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.41

Full CFAP206 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP206 p.Ala121Ser Uncertain significance ★ ⚠ same type
CFAP206 p.Ala213Val Uncertain significance ★ ⚠ same type
CFAP206 p.Ala255Thr Uncertain significance ★ ⚠ same type
CFAP206 p.Ala265Glu Uncertain significance ★ ⚠ same type
CFAP206 p.Ala265Val Uncertain significance ★ ⚠ same type
CFAP206 p.Ala393Val Uncertain significance ★ ⚠ same type
CFAP206 p.Arg114Gln Uncertain significance ★ ⚠ same type
CFAP206 p.Arg132Trp 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/cfap206-p-pro220leu (accessed [today's date]).

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