Is CFAP92 p.Glu16Lys (c.46G>A) pathogenic?

CFAP92 p.Glu16Lys (c.46G>A) is classified Uncertain significance in CFAP92 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-17). AlphaMissense: likely benign (0.1484); Ultra-rare (popmax 0.078%, sas).

How common is CFAP92 p.Glu16Lys (c.46G>A) in the general population?

CFAP92 p.Glu16Lys (c.46G>A) is ultra-rare (popmax 0.078%, sas) (gnomAD).

What do computational predictors say about CFAP92 p.Glu16Lys (c.46G>A)?

AlphaMissense predicts likely benign (score 0.1484) — an in-silico prediction, not a clinical call.

CFAP92 p.Glu16Lys

c.46G>A · VCV3266550

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1484 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.078%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1484	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -6.60	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.30	acceptor gain · deltas
Pangolin	Δ0.35	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -0.031	GERP -0.62
Regional constraint	o/e 0.94	unconstrained · MANE · 83 kb · p 0.026 · regional, not allelic
Overall
CADD	8.824	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

Grpmax group 0.078% South Asian · 71/91,078 alleles

Filtering AF 0.0633% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.058%

Overall 0.00551% 89/1,613,924 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.078%	1,283
Middle Eastern	0.033%	3,030
Remaining individualsnot grpmax-eligible	0.0064%	15,621
European (non-Finnish)	0.00102%	98,323

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: CFAP92
Protein: p.Glu16Lys
Coding: c.46G>A
MANE Select: NM_001394090
Type: single nucleotide variant
Location: chr3:128993259 (GRCh38)
Gene constraint: LOEUF 0.959 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.39

Full CFAP92 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACAD9 c.1692+1G>A Likely pathogenic ★★ same type
ACAD9 p.Arg532Gln Likely pathogenic ★★ ⚠ same type
ACAD9 p.Asn569His Uncertain significance ★★ ⚠ same type
ACAD9 p.Glu596Lys Uncertain significance ★★ ⚠ same type
ACAD9 c.1692+145G>C Benign ★★ same type
ACAD9 c.*26C>T Benign/Likely benign ★★ same type
ACAD9 c.*331T>G Benign/Likely benign ★★ same type
ACAD9 c.*68C>T 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/cfap92-p-glu16lys (accessed [today's date]).

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