Is CFAP206 p.Thr449Ile (c.1346C>T) pathogenic?

CFAP206 p.Thr449Ile (c.1346C>T) is classified Uncertain significance in CFAP206 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-30). AlphaMissense: likely benign (0.1913); Absent from gnomAD v4.1.

How common is CFAP206 p.Thr449Ile (c.1346C>T) in the general population?

CFAP206 p.Thr449Ile (c.1346C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CFAP206 p.Thr449Ile (c.1346C>T)?

AlphaMissense predicts likely benign (score 0.1913) — an in-silico prediction, not a clinical call.

CFAP206 p.Thr449Ile

c.1346C>T · VCV4001415

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1913 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,504,352)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1913	likely benign
REVEL	0.091	moderately benign-leaning
SaProt	LLR -7.04	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 2.2	GERP -0.21, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 54 kb · p 0.001 · regional, not allelic
Overall
CADD	17.21	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

No allele count reported in gnomAD v4.1 (AN 1,504,352). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CFAP206
Protein: p.Thr449Ile
Coding: c.1346C>T
MANE Select: NM_001031743
Type: single nucleotide variant
Location: chr6:87434905 (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-thr449ile (accessed [today's date]).

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