Is CFAP100 p.Gln496Arg (c.1487A>G) pathogenic?

CFAP100 p.Gln496Arg (c.1487A>G) is classified Uncertain significance in CFAP100 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-14). AlphaMissense: likely benign (0.0892); Ultra-rare (popmax 0.0783%, amr).

How common is CFAP100 p.Gln496Arg (c.1487A>G) in the general population?

CFAP100 p.Gln496Arg (c.1487A>G) is ultra-rare (popmax 0.0783%, amr) (gnomAD).

What do computational predictors say about CFAP100 p.Gln496Arg (c.1487A>G)?

AlphaMissense predicts likely benign (score 0.0892) — an in-silico prediction, not a clinical call.

CFAP100 p.Gln496Arg

c.1487A>G · rs749924924 · VCV2402690

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0892 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0783%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0892	likely benign
REVEL	0.069	moderately benign-leaning
SaProt	LLR -7.58	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.37 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.5	GERP -1.4, phastCons 0.78
Regional constraint	o/e 1.04	unconstrained · MANE · 40 kb · p 0.22 · regional, not allelic
Overall
CADD	9.885	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 0.0783% Admixed American · 47/59,998 alleles

Filtering AF 0.0604% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0542%

Overall 0.00297% 48/1,613,846 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0783%	1,277
Remaining individualsnot grpmax-eligible	0.0016%	62,480

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: CFAP100
Protein: p.Gln496Arg
Coding: c.1487A>G
MANE Select: NM_182628
dbSNP: rs749924924
Type: single nucleotide variant
Location: chr3:126434240 (GRCh38)
Gene constraint: LOEUF 1.041 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.85 · 1 PDB
Residue 496: the 'interaction with ttll13' region

Full CFAP100 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP100 p.Ala126Ser Uncertain significance ★ ⚠ same type
CFAP100 p.Ala179Val Uncertain significance ★ ⚠ same type
CFAP100 p.Ala224Asp Uncertain significance ★ ⚠ same type
CFAP100 p.Ala499Thr Uncertain significance ★ ⚠ same type
CFAP100 p.Ala563Val Uncertain significance ★ ⚠ same type
CFAP100 p.Ala565Val Uncertain significance ★ ⚠ same type
CFAP100 p.Ala73Pro Uncertain significance ★ ⚠ same type
CFAP100 p.Arg103Gln 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/cfap100-p-gln496arg (accessed [today's date]).

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