Is CFAP65 p.Gln134Ter (c.400C>T) pathogenic?

CFAP65 p.Gln134Ter (c.400C>T) is classified Pathogenic in CFAP65 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-28). Very rare (popmax 0.00667%, amr).

How common is CFAP65 p.Gln134Ter (c.400C>T) in the general population?

CFAP65 p.Gln134Ter (c.400C>T) is very rare (popmax 0.00667%, amr) (gnomAD).

CFAP65 p.Gln134Ter

c.400C>T · rs747889116 · VCV2066848

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 35
Splicing
SpliceAI	Δ0.25	acceptor loss · deltas
Pangolin	Δ0.27	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4.4	GERP -0.25, phastCons 0.99
Overall
CADD	34.0	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 0.00667% Admixed American · 4/59,990 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000248% 4/1,613,928 alleles · very rare

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: CFAP65
Protein: p.Gln134Ter
Coding: c.400C>T
MANE Select: NM_194302
dbSNP: rs747889116
Type: single nucleotide variant
Location: chr2:219035622 (GRCh38)
Gene constraint: LOEUF 0.85 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.03

Full CFAP65 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP65 p.Arg1231= Benign ★★ same type
CFAP65 p.Arg1545Gln Benign ★★ same type
CFAP65 p.Arg760Gln Benign ★★ same type
CFAP65 p.Asp1313= Likely benign ★★ same type
CFAP65 p.Leu1127= Benign/Likely benign ★★ same type
CFAP65 p.Leu1523= Benign/Likely benign ★★ same type
CFAP65 p.Leu1906= Benign/Likely benign ★★ same type
CFAP65 p.Lys1805= 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/cfap65-p-gln134ter (accessed [today's date]).

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