Is CFAP206 p.Leu326Phe (c.976C>T) pathogenic?

CFAP206 p.Leu326Phe (c.976C>T) is classified Uncertain significance in CFAP206 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-29). AlphaMissense: likely pathogenic (0.6028); Rare (popmax 0.127%, afr).

How common is CFAP206 p.Leu326Phe (c.976C>T) in the general population?

CFAP206 p.Leu326Phe (c.976C>T) is rare (popmax 0.127%, afr) (gnomAD).

What do computational predictors say about CFAP206 p.Leu326Phe (c.976C>T)?

AlphaMissense predicts likely pathogenic (score 0.6028) — an in-silico prediction, not a clinical call.

CFAP206 p.Leu326Phe

c.976C>T · VCV3491212

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6028 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.127%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6028	likely pathogenic
REVEL	0.282	benign-leaning
SaProt	LLR -8.99	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 0.41, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 54 kb · p 0.001 · regional, not allelic
Overall
CADD	24.0	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 0.127% African / African-American · 95/75,022 alleles

Filtering AF 0.106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0983%

Overall 0.00657% 106/1,614,072 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.127%	790
Remaining individualsnot grpmax-eligible	0.0096%	10,417
Admixed American	0.00667%	15,004
European (non-Finnish)	8.47e-05%	1,179,981

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.Leu326Phe
Coding: c.976C>T
MANE Select: NM_001031743
Type: single nucleotide variant
Location: chr6:87428641 (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-leu326phe (accessed [today's date]).

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