Is CFAP206 p.Asp454Tyr (c.1360G>T) pathogenic?

CFAP206 p.Asp454Tyr (c.1360G>T) is classified Uncertain significance in CFAP206 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-25). AlphaMissense: likely benign (0.1002); Ultra-rare (popmax 0.0116%, nfe).

How common is CFAP206 p.Asp454Tyr (c.1360G>T) in the general population?

CFAP206 p.Asp454Tyr (c.1360G>T) is ultra-rare (popmax 0.0116%, nfe) (gnomAD).

What do computational predictors say about CFAP206 p.Asp454Tyr (c.1360G>T)?

AlphaMissense predicts likely benign (score 0.1002) — an in-silico prediction, not a clinical call.

CFAP206 p.Asp454Tyr

c.1360G>T · rs375860563 · VCV3143352

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1002 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0116%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1002	likely benign
REVEL	0.105	moderately benign-leaning
SaProt	LLR -8.62	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.22	acceptor gain · deltas
Pangolin	Δ0.34	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 3.8	GERP -0.21, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 54 kb · p 0.001 · regional, not allelic
Overall
CADD	24.9	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 0.0116% European (non-Finnish) · 130/1,116,944 alleles

Filtering AF 0.00997% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00938%

Overall 0.00906% 139/1,534,566 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0116%	8,592
Remaining individualsnot grpmax-eligible	0.00669%	14,941
African / African-American	0.00412%	24,263
Admixed American	0.00355%	28,157

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.Asp454Tyr
Coding: c.1360G>T
MANE Select: NM_001031743
dbSNP: rs375860563
Type: single nucleotide variant
Location: chr6:87434919 (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-asp454tyr (accessed [today's date]).

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