Is CFAP300 p.Leu6Phe (c.16C>T) pathogenic?

CFAP300 p.Leu6Phe (c.16C>T) is classified Benign/Likely benign in CFAP300 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-26). AlphaMissense: likely benign (0.0564); Rare (popmax 0.204%, nfe).

How common is CFAP300 p.Leu6Phe (c.16C>T) in the general population?

CFAP300 p.Leu6Phe (c.16C>T) is rare (popmax 0.204%, nfe) (gnomAD).

What do computational predictors say about CFAP300 p.Leu6Phe (c.16C>T)?

AlphaMissense predicts likely benign (score 0.0564) — an in-silico prediction, not a clinical call.

CFAP300 p.Leu6Phe

c.16C>T · rs184947491 · VCV1681444

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0564 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.204%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0564	likely benign
REVEL	0.021	moderately benign-leaning
SaProt	LLR -7.45	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 0.28	GERP 1.2
Regional constraint	o/e 1.12	unconstrained · MANE · 36 kb · p 0.034 · regional, not allelic
Overall
CADD	5.584	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 0.204% European (non-Finnish) · 2,343/1,146,734 alleles

Filtering AF 0.197% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.195%

Overall 0.185% 2,841/1,535,916 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	2.52%	40
European (non-Finnish)grpmax	0.204%	489
South Asian	0.203%	492
Remaining individualsnot grpmax-eligible	0.2%	500
East Asian	0.139%	717
Admixed American	0.098%	1,020
Middle Eastern	0.0836%	1,196
Finnishnot grpmax-eligible	0.0809%	1,236
African / African-American	0.0437%	2,287
Ashkenazi Jewishnot grpmax-eligible	0.014%	7,161

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CFAP300
Protein: p.Leu6Phe
Coding: c.16C>T
MANE Select: NM_032930
dbSNP: rs184947491
Type: single nucleotide variant
Location: chr11:102047486 (GRCh38)
Gene constraint: LOEUF 1.386 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.21

Full CFAP300 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP300 p.Arg121Ter Pathogenic ★★ same type
CFAP300 p.Arg144Ter Pathogenic/Likely pathogenic ★★ same type
CFAP300 p.Gln160Ter Pathogenic ★★ same type
CFAP300 p.Gln52Ter Pathogenic ★★ same type
CFAP300 p.His259Arg Pathogenic/Likely pathogenic ★★ same type
CFAP300 c.110+16A>G Benign ★★ same type
CFAP300 c.192+59A>C Benign ★★ same type
CFAP300 c.268+13T>C Benign/Likely benign ★★ 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/cfap300-p-leu6phe (accessed [today's date]).

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