Is CFAP91 p.Gln415Ter (c.1243C>T) pathogenic?

CFAP91 p.Gln415Ter (c.1243C>T) is classified Uncertain significance in CFAP91 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-02). Ultra-rare (popmax 0.035%, amr); Associated with CFAP91-related condition.

What condition is associated with CFAP91 p.Gln415Ter (c.1243C>T)?

CFAP91 p.Gln415Ter (c.1243C>T) is associated with CFAP91-related condition (ClinVar).

How common is CFAP91 p.Gln415Ter (c.1243C>T) in the general population?

CFAP91 p.Gln415Ter (c.1243C>T) is ultra-rare (popmax 0.035%, amr) (gnomAD).

CFAP91 p.Gln415Ter

c.1243C>T · VCV3779824

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.035%, amr)

Conditions

CFAP91-related condition

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 10 of 18
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.45	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 4.1	GERP 0.59, phastCons 1
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.035% Admixed American · 21/60,016 alleles

Filtering AF 0.0234% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0197%

Overall 0.00273% 44/1,614,124 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.035%	2,858
Remaining individualsnot grpmax-eligible	0.008%	12,500
European (non-Finnish)	0.00144%	69,410
African / African-American	0.00133%	75,062

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: CFAP91
Protein: p.Gln415Ter
Coding: c.1243C>T
MANE Select: NM_033364
Type: single nucleotide variant
Location: chr3:119733405 (GRCh38)
Gene constraint: LOEUF 1.129 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.20 · 1 PDB

Full CFAP91 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CFAP91-related condition

Similar variants

CFAP91 p.Asp42His Uncertain significance ★ ⚠ same condition
CFAP91 c.359+1G>A Likely pathogenic ★ same type
CFAP91 p.Gln545Ter Likely pathogenic ★ same type
CFAP91 c.501-3T>C Uncertain significance ★ same type
CFAP91 p.Ala249Asp Uncertain significance ★ ⚠ same type
CFAP91 p.Ala256Thr Uncertain significance ★ ⚠ same type
CFAP91 p.Ala449Val Uncertain significance ★ ⚠ same type
CFAP91 p.Ala598Ser 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/cfap91-p-gln415ter (accessed [today's date]).

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